Embolisation systems

ABSTRACT

A bristle device (8) for delivery into a body lumen comprises a longitudinally extending stem and a plurality of bristles extending generally outwardly from the stem for anchoring the device in a body lumen. There may beat least two bristle segments (96) and there are flexible sections (95) between the segments (96). The flexible sections (95) articulate to enable the device to pass through a catheter placed in a tortuous anatomy or to be deployed in a curved vessel, or across a bifurcation. In some cases at least some of the bristle segments (96) are spaced-apart to accommodate bending of the bristles.

INTRODUCTION

This invention relates to devices and systems for embolisation.

Migration of conventional embolisation coils occurs 4-14% oftranscatheter embolisations [2,3]. Non-target embolisation is an outcomeof coils migration, the impact of which depends on the final location ofthe coils. In the venous system, the consequences can be catastrophicwith literature indicating that coils can migrate into the renal vein,right atrium of the heart, lung (pulmonary artery). Percutaneousretrieval of the coils is technically very challenging and frequentlycannot be attempted as the coils are often entrapped within the organsand tissue.

Coil migration occurs for various reasons:

-   -   Technical error: release of a coil or coil pack too distal or        proximal to an adjoining larger vessel or plexus [6,7]    -   High blood flow areas can cause the coil to migrate.    -   Coil: vessel mismatch. The coils are undersized, hence will not        injure the vessel wall, will not induce thrombosis, and are        likely to migrate. Or the coils are oversized and will act like        a guide-wire and pass further distally into the vessel [8,9].    -   Vessel dilation: coil migration can occur due to a disparity in        the size of coils and dilated vessels, which can change in their        diameters depending on vessel hemodynamics [5].    -   Coils impart a very low radial (anchor) force on the lumen, once        a clot forms within the coil, blood flow can force it to        migrate.

The profile of the embolisation device and delivery system is a criticalsuccess factor in successfully accessing target embolisation locationse.g. the iliac arteries are frequently tortuous in the presence ofabdominal aortic aneurysms [8]. To combat this issue today,microcatheters are often employed in difficult or tortuous anatomy whereuse of standard catheters may induce spasm and lead to a failedembolisation procedure [8]. Additionally different stages in a proceduremay require catheters with different mechanical properties e.g.accessing a visceral vessel, particularly in the presence of diseased ortortuous arteries, may require a catheter with a high degree ofstiffness and torque control. In general, the lower the profile of thedevice and delivery system, the greater the accessibility of the deviceinto tortuous and higher order vessels. A lower profile device reducesthe diameter of catheter required for delivery and lowers the risks ofaccess site infections, hematomas and lumen spasm.

Dependent on the clinical application of the device, variable anchorforces may be required to prevent migration of the prosthesis e.g.arterial and venous applications have variable blood flow rates andforces. This in turn, will lead to a compromise in terms of profilesince larger fibres, which better anchor the bristle device in thelumen, will require a larger catheter for delivery.

The technique generally used to embolise vessels today is to insert ametallic scaffold (coil, plug) into the target vessel, to cause athrombus that adheres to the scaffold, relying on the thrombus to induceblood cessation and eventually occlude the vessel. In general, availableembolisation technology does not interfere with or interact with bloodflow densely enough across the vessel cross section to induce rapid,permanent vessel occlusion.

Using technology available today, the physician will often have toprolong a specific duration of time for the technology to induceocclusion. In one approach the physician inserts coils and then waits 20minutes for the coils to expand and cause vessel occlusion [1].

The restoration of the lumen of a blood vessel following thromboticocclusion by restoration of the channel or by the formation of newchannels, is termed recanalisation. Recanalisation can occur due to,coil migration, fragmentation of the embolisation material, andformation of a new vessel lumen that circumvents the occlusion [9].Recanalization rates vary by procedure and embolic agent, ranging from10% to portal vein embolisation to 15% for pulmonary arteriovenousmalformations to 30% for splenic artery embolisation [12,14,15].

U.S. Pat. No. 5,573,547 describes a brush fixation method for attachmentof tissues and occlusion of blood vessels.

STATEMENTS OF INVENTION

According to the invention there is provided an embolisation device forpromoting clot formation in a lumen comprising a stem and a plurality offlexible bristles extending outwardly from the stem, the bristles havinga contracted delivery configuration and a deployed configuration inwhich the bristles extend generally radially outwardly from the stem toanchor the device in a lumen, the device comprising a plurality ofsegments, each of which comprises a plurality of bristles and whereinthe device comprises flexible sections between at least some of thebristle segments.

In one embodiment the stem comprises flexible sections between thebristle segments. The flexible sections may articulate.

In one case a bristle segment in the deployed configuration has asegment diameter, a segment length and a bristle density defined by thenumber of bristles in the segment. The segment bristle density may befrom 100 to 1000 per centimetre of segment length. The segment bristledensity may be from 100 to 300, optionally 200 to 800, optionally 300 to800, optionally 200 to 1000 per centimetre of segment length. Thesegment diameter may be from 3 to 24 mm. The segment diameter may befrom 3 to 6, optionally 6 to 8, optionally 8 to 10, optionally 10 to 12,optionally 12 to 16, optionally 10 to 18, optionally 10 to 24 mm. Thesegment diameter may be from 4 to 5, optionally 6, optionally 12,optionally 15, optionally 16 mm. The segment diameter may be from 4 to6, optionally 8, optionally 15, optionally 17, optionally 22 mm. Thesegment length may be less than 8 mm, optionally from 3 to 7, optionallyfrom 3 to 6, optionally from 3 to 4, optionally from 4 to 5 mm.

In some cases the diameter of the bristles is from 0.001 to 0.005inches. The bristles may be from 0.001 to 0.002, optionally 0.002 to0.003, optionally 0.002 to 0.004 inches. The stem may comprise a wirehaving a diameter of from 0.003 to 0.012 inches. The wire diameter maybe 0.004, optionally 0.006 to 0.008, optionally 0.008 to 0.010,optionally 0.008 to 0.012 inches.

In one embodiment at least some of the segments are spaced-apart todefine a gap therebetween.

The length of the gap between adjacent segments may be from 1 mm to 10mm, optionally from 2 mm to 6 mm, optionally from 3 mm to 4 mm.

In one embodiment the embolisation device comprises a first group ofbristles and a second group of bristles, the second group of bristlesextending radially outwardly from the stem in the deployed configurationto a radial extent which is at least 1 mm, optionally at least 2 mm,optionally at least 3 mm, optionally at least 4 mm, optionally at least5 mm more than the radial extent of the first group of bristles.

The second group of bristles may be provided at a proximal end of thedevice and/or at a distal end of the device.

In some embodiments at least some of the bristles are of a shape memorymaterial such as Nitinol.

In one embodiment the device includes a flow restrictor having acontracted delivery configuration and an expanded deployedconfiguration. A flow restrictor may be located at a proximal end of thedevice and/or at a distal end of the device. The flow restrictor maycomprise a membrane. At least some of the bristles urge the flowrestrictor into the deployed configuration and/or the deliveryconfiguration. In some cases the flow restrictor is at least partiallyself expandable on movement between the delivery configuration and thedeployed configuration. The membrane may be impermeable. Alternativelythe membrane comprises openings such as radially extending slots. Insome cases the flow restrictor comprises a plurality of sections. Thesections of the flow restrictor may be spaced-apart along a longitudinalaxis of the device. In some cases the flow restrictor sections are ofdifferent diameters. The flow restrictor sections may be overlapped. Atleast a portion of the flow restrictor may be located between bristleson both sides of the restrictor. In some cases the flow restrictor inthe deployed configuration extends from the stem to a radial extentwhich is less than that of the bristles. The flow restrictor may be ofwind sock geometry and may have a distally facing opening. The flowrestrictor may be of balloon geometry. In some cases sealing means isprovided along the peripheral edge(s) of the flow restrictor.

In one embodiment at least some of the segments have loops and adjacentloops are interconnected to provide articulation between adjacentsegments. In one case a suture or monofilament material which is lessstiff than the stem is used to connect brush segments, providingimproved flexibility and articulation. A spring connection may beprovided between individual brush segments. The device may have means tolimit the maximum length of the device. In some cases the devicecomprises a ring to connect bristle brushes with looped ends. In oneembodiment the device comprises a wire or string connection, of a lowerstiffness than the bristle brush stem to accommodate bending of thedevice. In one case looped ends of the bristle brush stem are connectedby a connector element. In one case a wire/string element is wovenbetween a twisted wire stem of the bristle brush segment, thewire/string element being more flexible than the stem and emerging fromthe end of a bristle brush segment to connect to an adjacent bristlebrush segment and wherein a gap between adjacent bristle brush segmentsenables the wire/string element to accommodate deformations. In oneembodiment a thread type connection is provided between adjacent loopsof bristle brush segments. The device may comprise an elastic tubemounted to two adjacent bristle brush segments to facilitatearticulation between adjacent bristle brush segments. Adjacent bristlebrush segments may be connected by a braid. In one case adjacent bristlebrush segments are connected by a slotted tube, the slots being openableunder a bending load to accommodate articulation between segments.

In one embodiment there are at least two different groups of bristles.In one case the bristles of one group have a thickness which isdifferent than the thickness of bristles of another group. Alternativelyor additionally one group of bristles is of a different material thanthe material of another group of bristles. Alternatively or additionallyone group of bristles is more flexible than another group of bristles.Alternatively or additionally one group of bristles are interspersedwith another group of bristles. Alternatively or additionally one groupof bristles are adapted for anchoring the bristle device in a bodylumen. An anchoring group of bristles may be provided at the proximaland/or distal end of the device. In some cases one group of bristles areadapted for occlusion of a lumen. The occlusion group of bristles may belocated intermediate the proximal and distal ends of the bristle device.Some of the occluding group of bristles may be interspersed with theanchoring group of bristles so that the number of occluding bristlesincreases from the distal end towards the proximal end of the device. Inone embodiment some of the anchoring groups of bristles are interspersedwith the occluding group of bristles so that the number of anchoringbristles decreases from the distal end towards the proximal end of thedevice. In one case one group of bristles extend radially outwardly toone diameter and another group of bristles extend radially outwardly toanother diameter which is different than the diameter of the first groupof bristles. One group of bristles may be aligned differently thananother group of bristles.

In one embodiment at least some of the bristles are adapted for deliveryof a therapeutic agent. The agent delivery bristles are at leastpartially coated with a therapeutic agent. Alternatively or additionallyat least some of the bristles contain a therapeutic agent. In one casethe bristles comprise striations and/or holes for containing atherapeutic agent.

In one aspect the invention provides an embolisation bristle device forpromoting clot formation in a body lumen comprising a stem and aplurality of flexible bristles extending generally radially outwardlyfrom the stem, the bristles having a contracted delivery configurationand a deployed configuration in which the bristles extend generallyradially outwardly of the stem to anchor the device in a lumen, thedevice comprising a plurality of segments, each of which comprises aplurality of bristles, and wherein at least some of the segments arespaced apart to define spaces therebetween to accommodate bending of thebristles. This aspect may have some or all of the features mentionedabove and later in this specification.

The invention also provides a loading system for an embolisation bristledevice comprising a stem and a plurality of bristles extending outwardlyfrom the stem, the bristles having a contracted delivery configurationand a deployed configuration in which the bristles extend generallyradially outwardly of the stem to anchor the device in a lumen, thebristles, on deployment being oriented towards one longitudinaldirection. The loading system may be for deployment in a vein wherein,on deployment, the ends of the bristles are directed towards the heartto prevent migration. Alternatively the loading system may be fordeployment in an artery wherein, on deployment, the ends of the bristlesare directed away from the heart to prevent migration. The loadingsystem may comprise a loading tube having a distal end which can beconnected to a guide catheter. The loading system may comprise a loadingwire which is releasable attachable to the distal end of the bristledevice. The loading system may comprise a delivery wire which can attachto the proximal end of the bristle device for pushing the bristle devicethrough the loading tube and into a guide catheter for delivery to atarget vessel site. A distal end of the bristle device may beconnectable to the loading wire. A proximal end of the bristle devicemay be connectable to the delivery wire. In one case the distal end ofthe bristle device and the end of the loading wire has a loop and hookconfiguration for interconnection. In one case the proximal end of thebristle device has a threaded end. In some cases both the proximal anddistal ends of the bristle device are threaded.

Also provided is an embolisation bristle device loading systemcomprising a bristle device for delivery into a body lumen; a loadingtube; and a loading element for loading the bristle device into theloading tube. In one case the loading element is detachably mountable tothe bristle device. The loading element may comprise a loading wire. Theembolisation bristle device loading system may comprise a deliverycatheter for receiving the bristle device from the loading tube. Theloading element may be adapted for loading the bristle device from theloading tube into the delivery catheter. The loading element may beadapted for deploying the bristle device from the delivery catheter. Theembolisation bristle device loading system may comprise a taper or afunnel to aid loading of the bristle device into the loading tube and/orthe delivery catheter. The taper or funnel may comprise an extension ofthe loading tube.

In one embodiment the loading tube comprises means for re-orientating atleast some of the bristles of the bristle device as the bristle deviceis passing through the loading tube. In one case the re-orientationmeans comprises at least one hole in the wall of the loading tubethrough which the bristles may temporarily extend radially outwardly fortransition from a first configuration in which the bristles are alignedat a first angle to the longitudinal axis of the loading tube and asecond configuration in which the bristles are aligned at a second angleto the longitudinal axis of the loading tube. In the secondconfiguration the bristles may extend generally in an opposite directionto the orientation of the bristles in the first configuration. In onecase the re-orientation means comprises at least one slot in the wall ofthe loading tube.

Also provided is a method for loading an embolisation bristle deviceinto a delivery catheter comprising the steps of providing a bristledevice, a loading tube and a loading element; using the loading element,delivering the bristle device into the loading tube; and using theloading element, delivering the bristle device into a delivery catheter.

The method may comprise deploying the bristle device from the deliverycatheter using the loading element. The loading element is releasablymountable to the bristle device and the method comprises mounting theloading element to the bristle device for loading the bristle deviceinto the loading tube and/or for loading the bristle device into thedelivery catheter and/or for deploying the bristle device from thedelivery catheter, and/or for retrieving a deployed bristle device. Inone case after delivery of the bristle device into the loading tubeand/or into the delivery catheter and/or after deployment of the bristledevice, the loading element is detached from the loading element. Theloading element may be re-attached to the bristle device for retrievalof the bristle device.

In a further aspect the invention provides an embolisation device forpromoting clot formation in a lumen comprising a stem and a bundle offlexible bristles extending outwardly from the stem, the bristles havinga contracted delivery configuration and a deployed configuration inwhich the bristles extend generally radially outwardly from the stem toanchor the device in a lumen, the bundle of bristles in the deployedconfiguration having a diameter, a length and a bristle density definedby the number of bristles in the bundle and wherein the bristle densityis from 100 to 1000 per centimetre of segment length, the bundlediameter is from 3 to 24 mm, and wherein the longitudinal length of thebundle is less than 8 mm. The device may comprise a flow restrictor at aproximal end of the device and/or at a distal end of the device. In onecase the flow restrictor comprises a membrane which has a contracteddelivery configuration and an expanded deployed configuration. Thisaspect may have some or all of the features mentioned above and later inthe specification.

According to the invention there is provided a bristle device fordelivery into a body lumen comprising a longitudinally extending stemand a plurality of bristles extending generally radially outwardly fromthe stem wherein there are at least two different groups or types ofbristles.

In one embodiment bristles of one group have a thickness which isdifferent than the thickness of bristles of another group.

In one case one group of bristles is of a different material than thematerial of another group of bristles.

One group of bristles may be more flexible than another group ofbristles.

In one embodiment one group of bristles are interspersed with anothergroup of bristles.

In one case one group of bristles are adapted for anchoring the bristledevice in a body lumen. An anchoring group of bristles may be providedat the proximal and/or distal end of the device.

In one embodiment one group of bristles are adapted for occlusion of alumen. The occlusion group of bristles may be located intermediate theproximal and distal ends of the bristle device.

In one case at least some of the occluding group of bristles areinterspersed with the anchoring group of bristles so that the number ofoccluding bristles increases from the distal end towards the proximalend of the device.

In one embodiment some of the anchoring groups of bristles areinterspersed with the occluding group of bristles so that the number ofanchoring bristles decreases from the distal end towards the proximalend of the device.

In one case one group of bristles extend radially outwardly to onediameter and another group of bristles extend radially outwardly toanother diameter which is different than the diameter of the first groupof bristles.

According to a further aspect of the invention one group of bristles arealigned differently than another group of bristles.

At least some of the bristles may be adapted for delivery of atherapeutic agent. The agent delivery bristles may be at least partiallycoated with a therapeutic agent. Alternatively or additionally at leastsome of the bristles contain a therapeutic agent. In one case thebristles comprise striations and/or holes for containing a therapeuticagent.

In another aspect the invention provides a bristle device loading systemcomprising:—

-   -   a bristle device for delivery into a body lumen;    -   a loading tube; and    -   a loading element for loading the bristle device into the        loading tube.

In one embodiment the loading element is detachably mountable to thebristle device.

In one case the loading element comprises a loading wire.

The system may comprise a delivery catheter for receiving the bristledevice from the loading tube. The loading element may be adapted forloading the bristle device from the loading tube into the deliverycatheter. The loading element may also be adapted for deploying thebristle device from the delivery catheter.

In one embodiment the system comprises a taper or a funnel to aidloading of the bristle device into the loading tube and/or the deliverycatheter.

In one case the taper or funnel comprises an extension of the loadingtube.

In one embodiment the loading tube comprises means for re-orientating atleast some of the bristles of the bristle device as the bristle deviceis passing through the loading tube.

The re-orientation means may comprise at least one hole in the wall ofthe loading tube through which the bristles may temporarily extendradially outwardly for transition from a first configuration in whichthe bristles are aligned at a first angle to the longitudinal axis ofthe loading tube and a second configuration in which the bristles arealigned at a second angle to the longitudinal axis of the loading tube.In one case, in the second configuration the bristles extend generallyin an opposite direction to the orientation of the bristles in the firstconfiguration.

The re-orientation means may comprise at least one slot in the wall ofthe loading tube.

In a further aspect the invention provides a method for loading abristle device into a delivery catheter comprising the steps of:—

-   -   providing a bristle device, a loading tube and a loading        element;    -   using the loading element, delivering the bristle device into        the loading tube; and    -   using the loading element, delivering the bristle device into a        delivery catheter.

The method may comprise deploying the bristle device from the deliverycatheter using the loading element.

In one case the loading element is releaseably mountable to the bristledevice and the method comprises mounting the loading element to thebristle device for loading the bristle device into the loading tubeand/or for loading the bristle device into the delivery catheter and/orfor deploying the bristle device from the delivery catheter, and/or forretrieving a deployed bristle device.

In one case after delivery of the bristle device into the loading tubeand/or into the delivery catheter and/or after deployment of the bristledevice, the loading element is detached from the loading element.

In one embodiment the loading element is re-attached to the bristledevice for retrieval of the bristle device.

The invention also provides a bristle device which confirms to a vessellumen. The bristle device in this embodiment has a larger diameter thanthe target vessel but the bristles do not deliver sufficient force toperforate the vessel.

The invention further provides a bristle device which, when implantedimposes a greater resistance to flow in the axial direction compared tothe radial (lateral) direction.

In another aspect the invention provides the use of a bristle device tocause vascular occlusion for the treatment of haemorrhoids.

The invention also provides a bristle device for delivery into a bodylumen comprising a stem and a plurality of flexible bristles extendinggenerally radially outwardly from the stem wherein the device comprisesa plurality of segments, each of which comprises a plurality of bristlesextending generally radially outwardly from the stem, and wherein atleast some of the segments are spaced apart to define spacestherebetween to accommodate bending of the bristles.

This bending of the bristles enables the device to be deformed into acollapsed condition, so that the diameter in the collapsed condition issmaller than would be the case if such spaces were not present betweenthe segments.

The invention further provides a bristle device for delivery into a bodylumen comprising a stem and a plurality of flexible bristles extendinggenerally radially outwardly from the stem wherein the device comprisesa plurality of bristle segments, each of which comprises a plurality ofbristles extending generally radially outwardly from the stem, andwherein the device comprises flexible sections between at least some ofthe bristle segments.

In one case the stem comprises flexible sections between the bristlesegments.

In some embodiments the flexible sections articulate. The flexiblesections may articulate to enable the device to pass through a catheterplace in a tortuous anatomy, to enable the device to be deployed in acurved vessel and/or to enable the device to be deployed across abifurcation.

The flexible sections also enable the device to accommodate bendingduring physiological loading and thereby preventing fracturing.

In one case at least some of the segments have loops and adjacent loopsare interconnected to provide articulation between adjacent segments.

The stem may be constructed from wires twisted together and a region ofincreased flexibility is provided by discontinuing one of the wires,thus decreasing the stiffness between adjacent bristle segments.

In one embodiment a suture or monofilament material which is less stiffthan the stem is used to connect brush segments, providing improvedflexibility and articulation. The suture may be connected to the bristlesegments using a hypotube. The hypotube may be attached to the stem andsuture by crimping.

In another embodiment a spring connection is provided between individualbrush segments. This spring may be configured such that in the unloadedconfiguration it cannot compress

In another case the spring is configured to compress or elongate tofacilitate adjustment of the device length during deployment.

In one embodiment the device has a limiter to limit the maximum lengthof the device.

In one case the maximum extension of a spring-like connection is limitedby the inclusion of a tension wire, which is connected to each segmentof the bristle brush.

In another embodiment the spring may be configured such that the totaldevice length may be reduced but not increased.

In one case the device comprises a ring to connect bristle brushes withlooped ends. The ring may be of relatively stiff to provide a hinge typejoint. The ring may be relatively flexible such that the ring flexesduring bending of the device.

In one embodiment a wire or string connection, of a lower stiffness thanthe bristle brush stem, is used to accommodate bending of the device.

In one case looped ends of the bristle brush stem are connected by aconnector element.

In one embodiment a wire/string element is woven between a twisted wirestem of the bristle brush segment, the wire/string element being moreflexible than the stem and emerging from the end of a bristle brushsegment to connect to an adjacent bristle brush segment and wherein agap between adjacent bristle brush segments enables the wire/stringelement to accommodate deformations.

In one case a thread type connection is provided between adjacent loopsof bristle brush segments.

In one embodiment an elastic tube is mounted to two adjacent bristlebrush segments to facilitate articulation between adjacent bristle brushsegments.

In one case the elastic tube has an inner diameter which is smaller thanthe outer diameter of the bristle brush stem.

In another case the elastic tube is of a heat shrinkable material, whichwhen subject to heat reduces its diameter to adhere to the stem ofadjacent brush segments.

Adjacent bristle brush segments may be connected by a braid.

Adjacent bristle brush segments may be connected by a slotted tube, theslots being openable under a bending load to accommodate articulationbetween segments.

In a one embodiment at least some of the segments are spaced apart todefine spaces therebetween to accommodate bending of the bristles.

In another aspect the invention provides a loading system for a bristledevice comprising a stem and a plurality of bristles extending generallyradially outwardly from the stem, the bristles, on deployment beingoriented at least in part in one longitudinal direction.

For deployment in a vein, on deployment, the ends of the bristles aredirected towards the heart to prevent migration.

For deployment in an artery, on deployment, the ends of the bristles aredirected away from the heart to prevent migration.

In one embodiment the loading system comprises a loading tube having adistal end which can be connected to a guide catheter.

The loading system may comprise a loading wire which is releasableattachable to the distal end of the bristle device.

The loading system may comprise a delivery wire which can attach to theproximal end of the bristle device for pushing the bristle devicethrough the loading tube and into a guide catheter for delivery to atarget vessel site.

In one case a distal end of the bristle device is connectable to theloading wire.

Alternatively or additionally a proximal end of the bristle device isconnectable to the delivery wire.

In one case the distal end of the bristle device and the end of theloading wire has a loop and hook configuration for interconnection.

In one embodiment the proximal end of the bristle device may have athreaded end.

In another embodiment both the proximal and distal ends of the bristledevice are threaded.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will be more clearly understood from the followingdescription of an embodiment thereof, given by way of example only, withreference to the accompanying drawings, in which:

FIG. 1 is an illustration of a bristle device according to the inventionwith two types of bristles having different diameters;

FIG. 2 illustrates the device of FIG. 1 loaded into a tube;

FIGS. 3 and 4 illustrate bristles of different diameters;

FIGS. 5 to 8 illustrate bristle devices with bristles of differentdiameters;

FIG. 9 illustrates a bristle device with two types of bristles (dashed,continuous, interspersed and evenly distributed);

FIG. 10 illustrates the uniform anchoring force applied by the device ofFIG. 9;

FIG. 11 illustrates a bristle device in which two different types ofbristles are used;

FIG. 12 illustrates the variation in the anchoring force applied by thedevice of FIG. 11;

FIG. 13 illustrates another bristle device with a gradual variation inbristle density;

FIG. 14 is a diagram illustrating the variation in the force applied bythe device of FIG. 13;

FIGS. 15 and 16 are illustrations of another bristle device of theinvention in collapsed and unconstrained configurations;

FIGS. 17a to 17c illustrate the effect of time in the collapsedcondition on unconstrained geometry of a bristle device, when deployed;

FIGS. 18 to 24 illustrate a bristle device loading system according tothe invention in various configurations of use;

FIGS. 25 and 26 illustrate a tapered loading tube;

FIGS. 27 and 28 illustrate differing bristle orientations with respectto flow;

FIGS. 29 and 30 show a loading tube with a re-orientation featureaccording to the invention;

FIGS. 31 to 33 illustrate the loading tube of FIGS. 29, 30, in use;

FIG. 34 shows a bristle device with bristles pointing in opposeddirections;

FIG. 35 illustrates vessel perforation by portion of a bristle device;

FIG. 36 illustrates a bristle device with flexible fibres for vesselconformance;

FIGS. 37 to 39 illustrate alternative bristle devices with geometries toconform with particular vessel shapes;

FIG. 40 illustrates deformation of a vessel by a bristle device;

FIG. 41 illustrates a bristle device with length and diameterattributed;

FIG. 42 shows the negative effect of a low length to diameter ratio;

FIG. 43 illustrates a bristle device with a high length to diameterratio;

FIG. 44 illustrates a bristle device with distal anchoring fibres;

FIG. 45 shows the use of longer bristles at the ends acting asstabilisers;

FIG. 46 illustrates a bristle device with stabilisers on both ends;

FIGS. 47 to 49 illustrate a delivery system having a slot detachmentmechanism;

FIGS. 50 to 52 illustrate a bristle device with another detachmentfeature;

FIGS. 53, 54 and FIGS. 55, 56 illustrate bristle devices with furtherdetachment features;

FIGS. 57 and 58 illustrate a bristle device with non uniform bristlelengths;

FIGS. 59 and 60 illustrate another bristle device with a curved core anda diameter less than that of the target lumen;

FIGS. 61 and 62 show a further bristle device with a curved core and adiameter greater than that of the target lumen;

FIGS. 63 and 64 show a bristle device with a curved core and variablebristle lengths;

FIGS. 65 and 66 show a bristle device with bristles pointing inwardlyfrom a retaining wire;

FIG. 67 illustrates the effect of core diameter on flexibility;

FIG. 68 shows a bristle device with flexible sections and application tobifurcated vessels;

FIG. 69 illustrates the control of fluid using a bristle device;

FIGS. 70 to 72 illustrate the uses of bristle devices;

FIG. 73 are typical patterns of contact caused by coils;

FIGS. 74 and 75 illustrate the effect of oversizing on surface areadivided by a bristle device;

FIG. 76 illustrates the impact of bristle density on vessel damage;

FIG. 77 illustrates a denudation technique using a bristle device;

FIGS. 78 to 81 illustrate bristle devices for use in treatment of aseptal defect;

FIGS. 82 to 85 illustrate steps in deployment of the devices of FIGS. 78to 81;

FIGS. 86 and 87 illustrate a bristle device with length modifyingcomponents;

FIG. 88 illustrates deployment of the device of FIGS. 86, 87;

FIG. 89 shows a bristle device with a loosely wound core;

FIG. 90 shows techniques of pushing a delivery catheter to decreaseadjustable sections between bristle segments;

FIG. 91 illustrates bristle devices with a through flow path;

FIG. 92 depicts the flow path in a twisted bristle device;

FIG. 93 illustrates overlapping bristle sections to inhibit flow;

FIG. 94 shows another bristle device with fibres that increase involume;

FIG. 95 illustrates a bristle device with microfibers for improvedthromogenicity;

FIG. 96 shows an embolus detaching from a bristle device;

FIG. 97 illustrates a bristle device deployed to treat a cerebralaneurysm;

FIGS. 98 to 100 illustrate bristle devices with gaps to limit clotfragments;

FIGS. 101 to 104 show various bristle tips to prevent vessel perforationupon or after deployment;

FIG. 105 illustrates the assembly of a bristle device to a deliverywire;

FIG. 106 illustrates a bristle device deployed in a lumen;

FIGS. 107 to 109 show various retrieval systems for retrieving a bristledevice;

FIGS. 110 to 112 illustrates various degradable bristle devices;

FIG. 113 illustrates the manufacture of a twisted wire bristle device;

FIG. 114 shows a twisted wire device with varying core wire pitch;

FIG. 115 illustrates manufacture of a bristle device from a number ofsegments;

FIGS. 116 and 117 show another method of manufacture;

FIGS. 118 to 125 illustrate bristle devices with various drug deliveryfeatures;

FIGS. 125 and 126 illustrate the use of a bristle device of theinvention to treat haemorrhoids;

FIG. 127 is a perspective view of another embolisation device of theinvention;

FIGS. 128 and 129 are views of details of the device of FIG. 127;

FIG. 130 is a perspective view of another embolisation device of theinvention;

FIG. 131 are perspective views of another embolisation device in astraight configuration (a) and a bent configuration (b);

FIGS. 132(a) to 142(b) are perspective views of further embolisationdevices of the invention in configurations similar to FIGS. 131(a) and131(b);

FIG. 143 is a diagram illustrating the optimal orientation of bristlesto prevent migration in venous vessels;

FIG. 144 is a diagram illustrating the optimal orientation of bristlesto prevent migration in arteries;

FIG. 145 illustrates the attachment of a loading wire to a distal end ofan embolisation device of the invention;

FIG. 146 is an enlarged view of the connection at the distal end of thedevice;

FIG. 147 illustrates the attachment of a delivery wire to a proximal endof the embolisation device;

FIG. 148 is an enlarged exploded view of the connection at the proximalend of the device;

FIGS. 149 to 153 illustrate loading, delivery and deployment in anartery;

FIGS. 154 to 158 illustrate loading, delivery and deployment in a vein;

FIGS. 159 to 166 illustrate various configurations of anchoring segmentsand occluding segments;

FIGS. 167 and 168 illustrate tapering of fibre length;

FIG. 169 illustrates fibres which are shape set;

FIGS. 170 to 177 illustrate various embolisation devices in differentlocations of use;

FIG. 178 illustrates delivery of a number of segments from a catheter;

FIGS. 179 to 181 illustrate offsetting of the stem core;

FIGS. 182 and 183 illustrate the use of the device to prevent backflowof particles delivered during particle embolisation;

FIGS. 184 to 186 illustrate steps in one method for using the device;

FIGS. 187 to 190 illustrate one method of joining segments together;

FIGS. 191 to 200 illustrate various embolisation devices incorporating aflow restrictor;

FIG. 201 schematically illustrates electrospinning to position themicrofibers;

FIGS. 202 and 203 illustrate the effect of using small diameter andlarge diameter fibres;

FIG. 204 is an illustration of an embolisation device of the invention;and

FIGS. 205 to 208 are diagrams illustrating steps in an embolisationprocedure using a device of the invention.

DETAILED DESCRIPTION

Referring to the drawings and initially to FIGS. 1 to 8 thereof there isillustrated a bristle device for delivery into a body lumen. The bristledevice comprises a longitudinally extending stem 1 and a plurality ofbristles extending generally radially outwardly from the stem. In theinvention there are at least two different groups or types of bristles.

In one case a prosthesis with two or more bristle fibre diameters isprovided to ensure a low profile for the device when loaded in thecatheter 5, and with sufficient anchor force to prevent migration.Smaller diameter fibre bristles 2 are intended primarily to promote andenhance thrombogenicity, while larger diameter fibre bristles 3 areintended primarily to anchor the device in the lumen to preventmigration.

Lumen occlusion occurs due to thrombogenicity of the device, which is afunction of its surface area and its ability to cause stasis. For agiven volume of fibre material, many small fibres 2 can be moreefficiently fitted into a catheter than few larger fibres 3.

Similarly, small fibres 2 are more thrombogenic per unit volume thanlarger fibres 3; as for a given volume of fibre material, there will bea greater amount of surface area for multiple small diameter fibres,than a few large diameter fibres.

FIGS. 5 and 6 illustrate a bristle device 6 with low diameter fibres 2.This enables the device to be collapsed to a low diameter, ø₁. FIGS. 7and 8 illustrate a prosthesis 7 with larger diameter fibres 3, whichwill enhance the migration prevention properties of the prosthesis. Thecollapsed diameter, ø₂, of this prosthesis is larger than ø₁.

The bristle device of FIGS. 1 and 2 has a combination of both low andhigh diameter fibres 2, 3. This enables a compromise in profile to adiameter, ø₃, where ø₁<ø₃<ø₂. This approach provides good migrationprevention properties (from large diameter fibres 3) combined with goodthrombogenicity and low profile (from the smaller diameter fibres 2).

The different bristle types can be of the same or different materials.More than one bristle material could also be used instead of, or incombination with more than one bristle diameter.

FIG. 9 illustrates another bristle device 8 according to the inventionwhich in this case has two different types of bristle interspersed andgenerally equally distributed along the length of the device. Thedifferent types of bristles may be distinguished by their dimensions ormaterial, each contributing separately in terms of anchor force andocclusion. Because of the equal distribution, the anchor force isuniformly distributed along the bristle device length as illustrated inFIG. 10.

Various alternative arrangements of different types or groups ofbristles may be provided.

For example, FIGS. 11 and 12 illustrate a bristle device 9, of length L,in which two different types of bristle are used: one for the middlesection 10 and one for the ends 11, 12. In this case, the bristles atthe ends of the device have a higher diameter. These bristles areintended to anchor the prosthesis within the lumen. The middle sectioncontains a higher density of bristles with a lower diameter, and isintended to cause more interference with blood flow along with moresurface contact with the blood and consequently, occlusion of the lumen.

FIG. 13 illustrates a bristle device 15, which has two different typesof bristle. In this case the bristles with better properties foranchoring the device in the lumen are more densely located on the lefthand side of the bristle device and taper off towards the right handside of the device where the density of the bristles of the second typeof bristles is higher. This would be advantageous in a high flowscenario requiring extremely large number of small diameter bristles tocause occlusion. By having the anchoring bristles at the end only, theother end could contain the extremely high number of lower diameterbristles required to cause occlusion, without compromising profile.Because of the distribution, the anchor force is distributed along thebristle device length as illustrated in FIG. 14.

A bristle device 16 when manufactured has an unconstrained geometry asillustrated in FIG. 15, which is the desired shape. In order to bedelivered through a catheter the bristle device must spend some time ina collapsed condition in a catheter 17 as illustrated in FIG. 16.

Storage of a device in a collapsed condition can lead to shape-settingof a bristle device, particularly if the bristles are constructed from apolymer. Specifically, once the bristle device is deployed from thecatheter it may not return fully to its original shape. Shape-settingrefers to any change in shape, which is caused due to storage a catheterfor a prolonged period. In general, the longer the period of storage thegreater the degree of shape setting is likely to be. This is shownschematically in FIGS. 17 a to 17 c.

To counteract this problem, in the invention a loading system isprovided. The loading system comprises a loading tube 20. The purpose ofthe loading tube 20 is to allow the clinician to collapse a bristledevice 25 for delivery through a delivery catheter 26 immediately beforefor (temporary or permanent) implantation in a lumen. In this way thebristle device 25 will not spend a substantial amount of time in thecollapsed condition, minimising the potential for shape setting. Theloading system also comprises a loading element such as a wire 21 forloading the bristle device 25 into the loading tube 20.

The bristle device can be delivered through any suitable deliverycatheter 26. The steps for use of the loading system are as follows:

-   -   i. Bring bristle device 25 and delivery wire 21 in contact (FIG.        18)    -   ii. Screw the delivery wire 21 into the prosthesis 25 (FIG. 19)    -   iii. Using the delivery wire 21, pull the bristle device 25 into        the loading tube 20 (FIG. 20)    -   iv. Connect the loading tube 20 to a delivery catheter 26 (FIG.        21)    -   v. Push the bristle device 25 into the delivery catheter 26        using the delivery wire 21 (FIG. 22)    -   vi. Once the tip of the bristle device 25 is at the tip of the        catheter 26 (located at the distal point of the vessel intended        for implantation), holding the delivery wire 21 still, retract        the delivery catheter 26 to deploy the bristle device 25 (FIG.        23)    -   vii. Once satisfied with the position of the device 25, unscrew        the delivery wire 21 from the bristle device 25 to detach (FIG.        24)

Referring to FIGS. 25 and 26, in another embodiment, a loading tube 36of tapered geometry will allow the user to crimp down the bristle device25 to the collapsed state as it is pushed via the delivery wire into thecatheter for delivery to a vessel.

Referring now to FIG. 27 there is illustrated a bristle device 37 with adiameter larger than the lumen, deployed such that the bristles pointalong the direction of flow within the lumen. FIG. 28 shows a schematicin which a prosthesis 38 is deployed with the bristles pointing theopposite direction of the flow.

The force of the flow against the prosthesis could cause it to migrate.If the direction of flow (force) is opposite to the direction in whichthe bristles point along the lumen, the force required to move thedevice will be smaller than the case in which the direction of the flow(force) is the same as the direction along which the bristles point inthe lumen. This is due to the interaction of the tips of the bristleswith the vessel wall and the resulting friction—the tips of the bristleshelp anchor the prosthesis in the lumen if any movement of the devicebegins to occur.

As the direction of action of the flow may not always be predictable, itmay be preferable to ensure that, when deployed, the bristle device hassome bristles oriented in one direction, and other bristles oriented inthe opposite direction. A physician may wish to use different approachesto deploy the device, which may or may not lead to a desirable bristledirection with respect to the flow direction.

When a bristle device is pulled into a loading tube 20 to be pushed intoa delivery catheter 26, its bristles are aligned within the loading tubesuch that they point distally when in the catheter. This means that allbristles will point one direction when the prosthesis is deployed. Asexplained above, this means that the device will have lower force tomigration in one direction than the other.

In one embodiment of the invention a loading tube is provided which isconfigured to reorient at least some of the bristles while the bristledevice is being pushed into the delivery catheter.

Referring to FIGS. 29 to 34 in one case a loading tube 40 containsreorientation slots 41 which allow the bristles to spring out while thebristle device 25 is being pushed into the delivery catheter 26.Subsequently, as these bristles encounter the end of the slot 41 whilethe device is being pushed into the delivery catheter 26, they areforced to collapse and realign, pointing in the opposite direction tothe direction they had originally pointed.

The loading tube may be adapted to include a means to open or close thehole depending on the wishes of the physician to change or not changethe orientation of the bristles.

Ideally an embolisation device should interact with the entire surfacearea of the target lumen. This has multiple benefits:

-   -   Assists denudation of the endothelium of the lumen wall, which        is known to aid in lumen embolisation.    -   Occludes the lumen along its entire length and cross sectional        area thereby preventing recanalization via a collateral or        side-branch into the target lumen.    -   Leads to a permanent occlusion thus reducing the risk of        surgical failure and the requirement for a repeat procedure.    -   Greater interaction with the vessel wall helps lock the implant        in position thereby reducing the risk of implant migration.

Removing or damaging the endothelium has a critical role to play in theclotting cascade within a lumen. When the endothelium is removed, thenormally isolated, underlying collagen is exposed to circulatingplatelets, which bind directly to collagen, which is released from theendothelium and from platelets; leading to the formation of a thrombus.If the device does not provide adequate lumen conformance and coveragethen recanalization can occur. This coverage should be maximised notonly in terms of vessel cross section but also vessel wall area also. Inspermatic vein occlusion, a liquid (e.g. sclerosant, which has greaterlumen conformance and coverage capabilities than coils) results inhigher technical success and lower recanalization rates than coils alone[8]. However, damage to the endothelium should be done without causingvessel perforation. This could lead to catastrophic events such asinternal bleeding. This is shown schematically in FIG. 35.

In another aspect of the invention a bristle device is provided whichhas a larger unconstrained diameter than the target vessel and whichincorporates bristles which are flexible enough to conform to the vesselanatomy and which will not cause vessel perforation i.e. delivery forceto the vessel wall is not sufficient to perforate.

FIG. 36 shows a prosthesis 50 for deployment in a lumen 51 with avarying lumen diameter. When deployed in a lumen with a varyingdiameter, the device can conform to the variations in the lumen diameterwithout causing lumen perforation. This is due to the flexibility of thefibres of the prosthesis which, while providing an anchor within thelumen, are not too stiff to perforate the lumen.

The potential for the fibres to perforate the vessel is dependentprimarily on the fibre material, fibre diameter and the surface area ofcontact between the fibre and the vessel wall. A fibre with a lowstiffness may have the potential to perforate the vessel if itsstiffness is high enough due to a large diameter (and potentially asharp bristle tip).

The fibres may be of a radiopaque material to enable the physician tovisualise the device using x-ray.

Material Diameter Less Than: Nitinol <0.015 Platinum <0.015 StainlessSteel <0.015 Polyester <0.015 PTFE <0.01 Nylon (Polyamide) <0.015Polypropylene <0.015 PEEK <0.015 Polyimide <0.015 Pebax <0.015Polyurethane <0.015 Silicone <0.015 FEP <0.015 Polyolefin <0.015

FIGS. 37 to 39 illustrate various embodiments in which lumens withnon-uniform diameters may be treated using a prosthesis which hasconforming geometries. FIG. 37 shows a “dog-bone” shaped prosthesis 55.FIG. 38 shows a tapered prosthesis 56 suitable for a tapered lumen. FIG.39 shows a prosthesis 57 suitable for a lumen with a step-change indiameter.

Referring to FIG. 40 in another embodiment a bristle device 58 in whichat least some of the bristles are stiffer and impose the geometry of thebristle device on the vessel wall. This occurs because the diameter ofthe bristle device is larger than that of the target vessel.

A Method to Treat Haemorrhoids

Background

Hemorrhoids, often described as “varicose veins of the anus and rectum,”are a common condition in which the veins lining the anus or lowerrectum become swollen and inflamed.

Hemorrhoids are varicosities of the hemorrhoidal plexus (rectal venousplexus). This plexus communicates with the uterovaginal plexus anddrains, via the rectal veins, into the internal pudendal vein andinternal iliac vein. Although the exact cause of hemorrhoids remainsunknown, standing too long in an upright position exerts pressure on therectal veins, which often causes them to bulge.

There are two types of hemorrhoids: external and internal, which referto their location. External hemorrhoids develop under the skin aroundthe anus; if a blood clot develops in one of them (in a condition knownas thrombosed external hemorrhoids), a painful swelling may occur.External hemorrhoids are characteristically hard and sensitive, andbleed upon rupture. Internal hemorrhoids are sac-like protrusions thatdevelop inside the rectal canal. Painless bleeding and protrusion duringbowel movements are the most common symptoms of internal hemorrhoids;however, they may cause severe pain if they become completely prolapsed,or protrude from the anal opening.

Hemorrhoidectomy, the surgical removal of hemorrhoids, is recommendedfor third- and fourth-degree internal hemorrhoids (with or withoutexternal hemorrhoids). The two major types of hemorrhoidectomyoperations are the closed (Ferguson) hemorrhoidectomy and the open(Milligan-Morgan) hemorrhoidectomy. Both techniques are performed usinga variety of surgical devices, including surgical scalpel, monopolarcauterization, bipolar energy, and ultrasonic devices.

Complications associated with Hemorrhoidectomy include [17]:

-   -   Urinary retention following hemorrhoidectomy is observed in as        many as 30 percent of patients    -   Urinary tract infection develops in approximately 5 percent of        patients after anorectal surgery    -   Delayed hemorrhage, probably due to sloughing of the primary        clot, develops in 1 to 2 percent of patients; it usually occurs        7 to 16 days postoperatively. No specific treatment is effective        for preventing this complication, which usually requires a        return to the operating room for suture ligation.    -   Fecal impaction after a hemorrhoidectomy is associated with        postoperative pain and opiate use. Most surgeons recommend        stimulant laxatives, stool softeners, and bulk fiber to prevent        this problem. Should impaction develop, manual disimp action        with anesthesia may be required.

An alternative to hemorrhoidectomy is stapled hemorrhoidopexy, in whichan intraluminal circular stapling device resects and resets the internalhemorrhoid tissues. When the stapler is fired, it creates a circularfixation of all tissues within the purse string to the rectal wall. Ineffect, it will draw up and suspend the prolapsed internal hemorrhoidtissue.

This procedure is best utilized when offered to patients withsignificant prolapse, such as those with grade II, grade III, or IVinternal hemorrhoids. This procedure does not effectively treat mostexternal hemorrhoids, and often requires separate excision of theexternal component when performed on patients with combined disease.

Neither procedure is effective at inducing long-term relief. In arandomized trial of stapled hemorrhoidopexy versus hemorrhoidectomy, theprocedures were equally effective in preventing recurrence after oneyear [18]. Patients undergoing hemorrhoidectomy were more likely to havesymptomatic relief from the hemorrhoids (69 versus 44 percent withhemorrhoidopexy), but had significantly greater postoperative pain [18].

It has been demonstrated that embolisation of the internal iliac veinsremoves reflux from hemorrhoidal plexus. Some dimishment and/ordisappearance of hemorrhoids has been associated with embolisation ofrefluxing pelvic and internal iliac veins (16). Technical success ofembolisation of the internal iliac or hypogastric veins has beenreported to be 85% [9,10].

In the clinical literature, caution has been advised when embolising theinternal iliac vein tributaries where there is clinically significantcommunication with veins of the lower limb; as this communicationbetween the obturator and the common femoral veins increases the risk ofcoil migration and displacement into a deep vein [5]. Displacement intoa deep vein can have serious consequences if the coil led to a deep veinthrombosis [5]. Accordingly, a safe and effective device is stillrequired for embolisation of the internal iliac veins for the treatmentof hemorrhiods.

In one aspect of the invention a method for the treatment ofhaemorrhoids is proposed in which a bristle device is implanted in theinternal iliac, or hemorroidal veins to cause permanent occlusion. Thisocclusion will prevent venous reflux to the hemorrhoidal plexus, whichcauses hemorroids.

FIG. 125 is a schematic showing the venous anatomy relating to thepresence of a haemorrhoid (detailed view of cross section of anus). Thebroken arrows show direction of venous reflux through internal iliacveins leading to varicosities off the haemorrhoidal plexus, causinghaemorrhoids.

FIG. 126 illustrates the insertion of bristle devices in internal iliacveins has arrested refluxing flow to the haemorrhoidal veins and causedthe haemorrhoid to disappear.

FIG. 41 shows a bristle device 60 with a length, L, and a diameter, ø.The stability of the device during and after deployment from a catheteris dependent upon the ratio of these quantities with respect to thevessel diameter. Ideally, the bristle device should have a diametergreater than or equal to the target lumen, and a length to diameterration, L/ø, of 1.0 or greater.

FIG. 42 shows a bristle device 61 with a ratio L/ø<1 deployed in alumen. The prosthesis has become unstable during, or after, deploymentand consequently now lies at an angle to the long axis of the lumen. Dueto a L/ø ratio <1 the device could migrate, recanalise or damage thelumen wall. The low length to diameter ratio also means that theprosthesis could “pop” out of the catheter making it difficult to deployaccurately to the target site.

FIG. 43 shows a bristle device 62 according to the invention withL/ø>1.0. In this case the prosthesis is correctly aligned, is stable andis unlikely to migrate or cause damage to the lumen wall.

Referring now to FIGS. 44 and 45 in this case a bristle device 63 haslonger bristles at the distal end (the end which will be deployed firstfrom the catheter). These longer bristles are intended to act as“stabilisers” upon initial partial deployment of the prosthesis. Thelonger bristles extend distally along the vessel wall providing andanchor, ensuring the prosthesis cannot “pop” forward from deliverycatheter upon completion of deployment.

The prosthesis may have stabilising bristles 65 at one or both ends of aprosthesis 64 as illustrated ion FIG. 46.

FIG. 47 shows a bristle device 71 in the collapsed configuration withina delivery catheter 72. A slot mechanism 70 is incorporated to enabledetachment once the device is fully deployed. The slot detachmentmechanism 70 may be radiopaque to enable the physician to establish theposition of the mechanism with respect to the catheter tip. FIG. 48shows the bristle partially deployed. In this configuration the slotdetachment mechanism is still engaged since the bristle device cannotmove off the axis of the delivery catheter and wire. Accordingly thephysician may still retract the bristle device at this point. FIG. 49shows the bristle device in the deployed configuration. Since thebristle device has exited the catheter it is not constrained to remainon the same axis of the delivery wire and becomes disengaged from thedelivery wire.

In another embodiment, and referring to FIGS. 50 to 52 a delivery wirewith a normally open grasping mechanism 75 illustrated. The graspingmechanism is designed to fit snugly around a ball end or lip 76 on abristle device 77. This mechanism 75 will always be open if notconstrained by the catheter wall. Once the bristle device has beenpushed out of catheter, the grasping mechanism 75 pops open detachingthe bristle device. Until this point the device can be retracted.Equally this type of mechanism could be used to retrieve the detachedbristle device by forcing the normally mechanism closed as it isretracted into the catheter.

FIG. 52 illustrates a bristle device with ball features 76 on both ends.

FIGS. 53 and 54 show a bristle device with a hook type mechanism 80 fordetachment and retrieval. The bristle device may have a hook at one, orboth ends. To ensure that lumen perforation cannot occur, the hook enddoes not project towards the lumen wall, but towards the bristle portionof the device instead.

FIGS. 55 and 56 show a bristle device with a loop type mechanism 81 fordetachment and retrieval. The bristle device can have a retrievalmechanism at one, or both ends. In this embodiment, the retrieval loopis created by forming the end of the twisted wire of the bristle burn.

FIG. 57 shows a bristle device 85 with non-uniform bristle lengths aboutthe circumference and along the device length. Variations in the bristlelength will reduce the potential for bristle device migration. FIG. 58shows the device of FIG. 57 deployed in a lumen.

-   -   Shorter bristles are less likely to buckle and can therefore        transmit a greater load to the lumen wall, increasing the radial        or “anchor” force of the device in the lumen, particularly        within non-uniform lumen diameters.    -   Imposition of undulations, roughness and non-uniformity in the        lumen wall will increase the resistance to migration of the        device due to increased friction.

FIG. 59 shows a bristle device 87 with a curved core or stem. In apreferred embodiment the core is helical, and the diameter of the helixis less than the diameter of the lumen. This configuration forces thebristles against the lumen wall, such that the radial force of thebristle device is not dependent on the outward force of the length anddiameter of the bristles alone, but also on the distance subtended bythe core to the lumen wall. This will increase the anchor force locallyand cause undulations/roughness in the lumen wall increasing theresistance to migration. FIG. 60 shows the bristle device 87 deployedwithin the lumen.

FIGS. 61 and 62 illustrate a bristle device 88 in which a core wire iscurved and the external diameter of the core is greater than that of thelumen. This configuration forces both the bristles and the core wireagainst the lumen wall. In this case the radial force of the bristledevice is a combination of both bristle and core, but is dominated byoutward force of the core.

FIGS. 63 and 64 illustrate a bristle device 89 with a curved core andnon-uniform bristle length. In this configuration, the bristle device isconfigured such that the bristle device has a curved core, and variablebristle lengths about the circumference and along the length.

FIGS. 65 and 66 illustrate another embodiment of a bristle device 90 inwhich all bristles point inward from a retaining wire. In this case thedevice is anchored entirely by the core/retaining wire.

To enable the physician to deliver the bristle device through tortuousanatomy it must be flexible. This also enables the bristle device toconform to tortuous anatomy once implanted. The flexibility of theprosthesis is defined, primarily, by properties of the core to which thebristles are attached. The flexibility of the core is a function notonly of the amount of material in the core, but also its distribution,and material (lower modulus means greater flexibility).

There are certain clinical indications where the optimal clinicaloutcome would be to simultaneously embolise a vessel and an adjoining,diverging division.

Such a clinical situation is the prophylactic embolisation to preventtype II endoleak pre-endovascular aneurysm repair (EVAR). Type IIendoleaks can be identified during angiography by the presence ofcontrast travelling from a peripherally catheterized vessel into theexcluded aneurysm sac. The objective when embolising pre-EVAR ispermanent occlusion of the internal iliac artery proximal to itsbifurcation to ensure that there is complete occlusion before proceedingto EVAR, as any leak will cause reoccurrence of the issue. Using anangled, adjacent vessel to anchor a portion of the device whiledeploying the majority of the same device in the larger vessel wouldprovide an anchor for the device, preventing future migration.

Additionally, the internal iliac vein bifurcates into anterior andposterior divisions, which supply pelvic organs as well as the glutealmuscles. It is frequently necessary to embolise one of the anterior orposterior divisions as well as the internal iliac vein. The sameapproach as described previously would be advantageous; embolising theadjacent tributary while retracting the remainder of the device toocclude the higher order vessel.

A bristle device, which has the flexibility to be deployed acrossbifurcating vessels, may be preferable in these instances.

FIG. 67 illustrates two device prostheses of the same length withdifferent core wire diameters, ø₁ and ø₂, where ø1>ø₂, Note: it isassumed that the core is approximately of circular cross section. Oneend of the prostheses is fixed and a load, P, is applied to the oppositeend causing deflection of the prosthesis. The deflection of the largerdiameter device, U1, is much smaller than that of the lower diameterdevice (U2).

Considering a bristle device with a stainless steel core constructedfrom twisted wire, its diameter should preferably be constructed fromtwisted wires of diameter 0.02 inches or less. Otherwise it may not bepossible to track the device to the target vessel for deployment.

In other embodiments, the flexibility of the device could be improved byhaving flexible sections 95 between device sections 96 as shown in FIG.68. Bending within the device is taken up, primarily, by the flexiblesections, which can articulate to enable it to pass through a catheterplaced in tortuous anatomy, or to be deployed in a curved vessel, oracross a bifurcation. In this case the bristle device has flexiblesections for articulation

Directional control of fluids (e.g. contrast media for angiographicvisualization, sclerosant for vessel embolisation) cannot be achievedwith today's embolisation technology. Currently the physician haslimited control over fluid dispersion. The current technique involvesflushing the fluid through the lumen of a catheter proximal to thetarget location.

This is of significant relevance in male and female varicoceleembolisation. A varicocele is a varicose dilation of the pampiniformplexus that drains the testicle and epididymis. The pampiniform plexusdrains into the internal spermatic vein. Additional small veins draininto saphenous, external iliac, and internal iliac systems.

For specific embolisation procedures e.g. varicocele, additional coilsmust be deployed in the cephalad portion of a vessel to ensure that thatthe coils occlude the main branch and all accessible collaterals [7]. Tominimize the risk of recurrence, it is often necessary to isolate themost distal (caudal) segment of the target vessel from any potentialcollateral supply. An alternative to coils is to use an occlusionballoon.

Furthermore in some patients, collateral parallel channels must beselectively catheterized and occluded, either with coils, scleroscant,glue or other embolic agents. When using sclerosants, the intention isto destroy the endothelium to expose subendothelial tissues that in turnwill lead to irreversible vascular fibrosis. For certain embolisationprocedures, e.g. varicocele, if the scleroscant migrates too distallyadverse effects can occur e.g. approximately 10% of males developtesticular phlebitis [8].

The sclerosant effect largely depends on a) the time it is in contactwith the endothelium and b) the volume and rate of injection [8].Controlling these variables significantly influence the outcome and alsothe propensity to damage adjacent non-target vessels.

This proximal migration of the fluid is often referred to as reflux. Insome cases, this fluid may contain a drug, sclerosant, fibrin, thrombin,glue, alcohol, beads, or drug coated beads. The physician may requireaccurate delivery of these agents to prevent non-target therapy.

In the invention a bristle device may be used to prevent proximalmigration of a fluid during delivery using a catheter.

When implanted, a bristle device causes a resistance to flow through thedevice. Similarly, the construction of the device itself means that flowis initiated within the device itself, the flow will have a lowerresistance laterally than axially, and will be inclined to fill up anyavailable space outside of the device rather than travel axially throughthe device itself. Consider the following steps in order to inject afluid into a vessel, wherein the direction of the flow is controlledusing a bristle device.

-   1. A bristle device is deployed distal to the location in which it    is intended to deliver the fluid-   2. The bristle device is crossed using a catheter such the tip of    the catheter resides on the distal side of the bristle device.-   3. The fluid is injected through the catheter tip. It is prevented    from migrating through the bristle device and will fill any vessels    distal to the device.

FIG. 69 illustrates a bristle device 97 in use to prevent proximalmigration of a fluid during delivery using a catheter.

In another embodiment, without the presence of individual bristlesegments, the path of least resistance for flow is still laterally. Thisis because the density of bristles laterally is lower than thatproximally and distally. Accordingly, the flow will naturally belaterally from the catheter tip. This enables treatment of a collateralvessel and is shown schematically in FIG. 71. FIG. 71 illustrates theuse of a bristle device 98 to ensure lateral dispersion of a fluid.Note: Section A-A shows a much higher density of fibres meaning flowwill have a higher resistance in this direction (axially) compared tolaterally (Section B-B).

The presence of these gaps between the brush segments is also a means toreduce the profile of the bristle device when constrained for placementin a catheter. This is because effect of bristles lying on top of oneanother, increasing profile is limited.

Referring to FIG. 72 in another embodiment, to further improve theability of a bristle device 99 to prevent longitudinally flow (ensurelateral dispersion of a fluid), bristles with a rectangular crosssection 100 are illustrated. The bristles are aligned such that the longaxis of the bristle is perpendicular to the centreline of the mainvessel. These bristles mean that the path of least resistance islaterally rather than distally or proximally. This can be observed byviewing Section A-A and B-B in FIG. 72. Clearly, it will be easier for afluid to pass through B-B than A-A due to the geometry of the bristles.

A blood vessel wall is composed of three layers. The innermost layer iscalled the endothelium and is merely a layer of endothelial cells. Themiddle and outer layers are known as the medial and adventitial layersrespectively.

It has been shown that denudation, or damage to the endothelial liningof a blood vessel can induce vasospasm, and inflammatory reactionsleading to vessel occlusion. Removing or damaging the endothelium has acritical role to play in the clotting cascade within a vessel. When theendothelium is removed, the normally isolated, underlying collagen isexposed to circulating platelets, which bind directly to collagen, whichis released from the endothelium and from platelets; leading to theformation of a thrombus.

Preferably, in order to induce the greatest damage to the endothelium, abristle device should have a large number of fibres in contact with thelumen wall per unit surface area. Embolisation coils do not causesignificant denudation to the vessel wall as the degree of wall contactis minimal. This can be seen in FIG. 73.

In order for a bristle device 101 to cause significant denudation of avessel wall it should have a greater diameter than the vessel in whichit is implanted. This ensures a larger contact area between fibres andthe vessel wall as shown in FIGS. 74 and 75.

Similarly, a greater number of fibres in contact with the vessel wallwill have a greater impact in causing denudation and inducingembolisation. This is shown schematically in FIG. 76. This can beexpressed in terms of the bristle length or area in contact with thevessel wall, per unit surface area of the vessel wall.

In some embodiments of the invention we provide

-   -   a bristle device for embolisation with a device diameter to        vessel diameter ratio of 1.1 or greater and/or    -   a bristle device a minimum length of bristle of 1 mm in contact        with a vessel surface area of 2 mm² and/or    -   a minimum of 0.1% of the vessel surface area in contact with the        bristle device fibres.

In another embodiment, the bristle device could be used for denudationof the vessel wall by advancing, retracting and rotating the bristledevice at the site of treatment. Once denudation is complete, theprosthesis can be left behind to promote permanent occlusion. FIG. 77 isa schematic showing denudation of the endothelium using translation androtation of a bristle device 105. This “polishing” action will helpstrip the endothelial cells from the vessel and enhance the potentialfor vaso-occlusion. Once complete the prosthesis can be detached fromthe delivery wire and left in place.

The bristle devices of the invention are also suitable for the treatmentof septal defects and patent foramen ovale.

Emboli leading to stroke or to transient ischemic attack can originatein either the systemic venous circulation (paradoxical emboli) or in thesystemic arterial circulation. Some patients with cryptogenic strokehave a patent foramen ovale (PFO), an atrial septal defect (ASD), or anatrial septal aneurysm (ASA) that can be identified by echocardiography.These structures have been implicated in the pathogenesis of embolicevents, leading to stroke.

Paradoxical emboli: a paradoxical embolus originates in the systemicvenous circulation and enters the systemic arterial circulation througha PFO, atrial septal defect, ventricular septal defect, or extracardiaccommunication such as a pulmonary arteriovenous malformation [10]. Theembolus can originate in veins of the lower extremities, in pelvicveins, in an atrial septal aneurysm, or from a clot around the edges ofa PFO [10]. Patients with paradoxical emboli can present withcryptogenic stroke.

PFO and ASD: The foramen ovale and its flap-like valve between the rightand left atrium are important components of the fetal circulation. Inthe developing fetus, oxygenated blood from the umbilical vein entersthe right atrium via the inferior vena cava and is shunted into the leftatrium, circumventing the non-inflated lungs. After birth, a relativeincrease in left atrial pressure closes the flap, and adhesionsfrequently result in a structurally intact atrial septum. However, inapproximately 25 percent of adults, the foramen ovale remains patent andacts as a potential right-to-left shunt [10].

The closure devices commonly used for percutaneous PFO repair includeoccluders made of two wire mesh discs filled with polyester fabric. Thedevice is folded into a special delivery catheter, advanced into theheart and through the defect. When the catheter is in the properposition, the device slowly is pushed out of the catheter until thediscs of the device sit on each side of the defect, like a sandwich. Thetwo discs are linked together by a short connecting waist. Over time,heart tissue grows over the implant, and it becomes part of the heart.

Complications associated with trans-catheter closure of a PFO/ASDinclude device embolisation or malposition, arrhythmias (usually atrialbut include sudden death), and device erosion/perforation [11].

Referring to FIG. 78 a bristle device 110 suitable for occlusion septaldefects of a patent foramen ovale is shown. The bristle device comprisesat least two distinct device sections, which are connected via a core.Referring to FIG. 79, the device 110 is shown in a tilted configurationhighlighting the flexibility of the device. This flexibility will enablethe device to conform to the anatomy of the patient, and will ensuregood trackability of the device during delivery. The bristle device 110can be used for septal defect and PFO occlusion. FIGS. 78 and 79 show aseptal defect or PFO device 110 which can articulate/bend depending onthe target anatomy.

FIGS. 80 and 81 illustrate a septal occlusion device 115, which canstretch depending on the target anatomy (thickness of the septal wall).

Referring to FIGS. 82 to 85 the implantation of the device 110 or 115 isillustrated. In FIG. 82 a catheter is shown advanced through the rightatrium via the inferior vena cava. In FIG. 83 a segment of the device isshown partially deployed. This first segment will provide an anchor onthe left atrium side of the patent foramen ovale. FIG. 84 illustratesone segment of the bristle device fully deployed within the left atrium.FIG. 85 illustrates the bristle device fully deployed.

Current technology foreshortens significantly upon deployment into avessel, between 30-50%, this intended approach attempts to ensure thatthe pre-shaped coil snaps into its set shape when deployed into a vesseland adheres to the vessel wall [13].

With the exception of glue, which is occasionally used, there is notechnology on the market today that does not use this approach.

Therefore it is difficult to embolise the entire length of a largevessel (>10 cm) with technology available today as complete vesselocclusion cannot be achieved and is cost prohibitive.

Additionally there is no product on the market today that canaccommodate variable lengths peri-procedurally. This would beadvantageous for three reasons:

-   -   Significantly reduce inventory requirements and range of        products to be manufactured    -   Allows the physician to precisely occlude the portion of the        vessel that requires occlusion    -   Allows a physician to occlude a bifurcation, feeder vessel or        tributary that may contribute towards recanalization

FIGS. 86 and 87 illustrate a bristle device 120 with length modifyingcomponents 121 that can be extended or retracted intraluminally toadjust the device to the requirements of the target vessel

FIG. 88 illustrates deployment of a first bristle bundle into the lumenof the target vessel. Also illustrated is a technique of retractingdelivery catheter to extend adjustable section between bristle bundles.

FIG. 89 illustrates an alternative embodiment depicting a loosely woundcore 125 that accommodates compression of bristle bundles intraluminally

FIG. 90 illustrates technique of pushing a delivery catheter 126 forwardto decrease adjustable sections between bristle bundles.

In order to induce stasis and cause thrombus formation, ideally nothrough flow path should exist in the prosthesis that permits blood toflow uninhibited from one end to the other. In reality, some flow pathmay exist which forces the blood to travel a tortuous path past theprosthesis bristles. If a low resistance flow path is present, occlusionmay not occur.

For a bristle device, manufactured using a twisted wire approach, thebristles effectively define a helical surface. The negative of thishelical surface defines a flow path.

By its nature, a bristle device may have a through flow path as shown inFIG. 91(a). This will cause turbulent flow and force the blood tointeract with a greater surface area of the device, inducing thrombusformation and occlusion. A more tortuous path is shown in FIG. 91(b).

FIG. 91 illustrates a bristle device 130 with a through flow path. Pathis shown adjacent to the bristle device using the arrow. This path couldbe described as the inverse of volume of the device. This tortuosity ofthis flow path is defined by the pitch and radius of the helix, whichdefines the flow path as shown in FIG. 92.

A longer pitch, p, with a small radius, r, will mean a relatively easyand straight flow path. A short pitch with a large radius will imply alonger tortuous flow path. If a flow path does exist, this should be astortuous and as long as possible to cause occlusion.

Preferably, for inducing occlusion of a blood vessel, the ratio of thepitch to the radius, p/r, of the flow path should be 50 or less. Morepreferably, the ratio of the pitch to the radius, p/r, of the flow pathshould be 10 or less. More preferably, the ratio of the pitch to theradius, p/r, of the flow path should be 1 or less. More preferably, theratio of the pitch to the radius, p/r, of the flow path should be 0.5 orless.

If a twisted wire manufacturing approach is used, the ratio of the pitchto the radius of the helix should be such that the adjacent bristlesections of a bristle device 140 overlap as shown in FIG. 93.

FIG. 93 illustrates overlapping bristle sections to inhibit flow paththrough device.

Another means of ensuring overlapping bristles is to form the deviceusing pre-shaped bristles e.g. saw tooth or spiral, which would increaseinteraction between bristles.

In FIG. 94 a bristle device is shown in which, upon coming in contactwith a fluid or blood, the fibres 150 swell up increasing in volume inorder to further occlude the lumen in which they reside. This processcould be initiated before deployment in the body, or while the bristledevice is in its collapsed condition in a catheter/loading tube, asshown in FIG. 94. Similarly, the fibres could be intended to absorb adrug when increasing in volume. This drug would then be delivered to thevessel wall once the bristle device is deployed. FIG. 94 illustratesfibres that increase in volume when in contact with a fluid and or theblood.

In another embodiment, the bristles could have micro fibres 160 in orderto increase thrombogenicity and reduce flow path. This is shownschematically in FIG. 95.

Due to adjacent vessel blood flow, an embolus could break away from theclot within the bristle device. The maximum potential size of an emboluswhich could break away from the bristle device is dictated by thedensity of the bristles in the device, i.e. the cavities within whichthrombus can form in the device. This is defined by the distance betweenadjacent bristles. Similarly, the ability of the bristle device to causevessel occlusion can be improved by reducing the distance betweenadjacent bristles.

Pulmonary Embolism

A common vessel for embolisation is the gonadal vein (for the treatmentof varicocele, pelvic vein competence). An embolus could detach from abristle device, which has been deployed in the proximal portion of agonadal vein close to the renal vein. This embolus can then travel viathe left common iliac vein through the inferior vena cava into the rightatrium of the heart. This could potentially travel into the pulmonaryarteries causing a pulmonary embolism. In about 5% of people in whomautopsy is done to elucidate the cause of death, pulmonary embolism isunexpectedly found to be the cause. Gardner suggests that the clot sizeshould be limited to 4.5 mm or less using clips in order to prevent alethal pulmonary embolism [19].

Peripheral Arterial

Ideally any embolus which could break away from the embolisation deviceis small enough so that it can be thrombolyzed by the body's owndefences and remain clinically asymptomatic. A large embolus could causetissue ischemia and infarction. In 1989, Kazmier proposed aclassification for disseminated peripheral atheroembolisation into threemajor clinical presentations: peripheral syndrome, renal syndrome, andvisceral syndrome [20]. By definition, microemboli representatheromatous material with a size less than 1 mm. Accordingly themaximum size embolus which can be permitted to break away from theocclusion device should be less than or equal to 1 mm. To ensure this,the maximum dimension between adjacent bristles which define the cavityfrom which an embolus could break away should be 1 mm or less. Anembolus from a bristle device deployed in the internal iliac arterycould enter the common iliac and travel distally to the smaller lumenssuch as the popliteal and tibial or pedal arteries (shown in FIG. 64). Ablockage of these lumens can cause ischemia of the foot, a phenomenonknown as trash foot. FIG. 96 shows an embolus detaching from a bristledevice which has been deployed in the left internal iliac artery.

Cerebral

The effect of an embolus may not be confined to the peripheralcirculation. In the case of the cerebral lumens, an embolus of 1 mm orless may not be tolerated, as emboli of this size can cause a stroke.For aneurysm treatment, the maximum acceptable diameter should be lowerthan 1 mm. For the case of embolic filters, used to capture emboli whichoccur during carotid stenting, the pore sizes are approximately 0.8 mmin diameter [21]. Accordingly the gap between the bristles in thedeployed configuration should be 0.8 mm or less. FIG. 97—shows a bristledevice deployed to treat a cerebral aneurysm. An embolus has broken awayfrom the bristle device which could cause stroke.

In the invention, and referring to FIGS. 98 to 100 to prevent pulmonaryembolism a bristle device 170, 171, 172 has gaps between adjacentbristles to limit clot fragments to 4.5 mm or less. To prevent potentialfor peripheral microembolism the bristle device should have gaps betweenadjacent bristles of 1 mm or less. For the prevention of cerebralinfarction events, the bristle device should have gaps between adjacentbristles of 0.8 mm or less.

FIGS. 98 to 100 illustrate gaps between bristles dictate the potentialemboli which could detach form the bristle device. A=4.5 mm, B=1.0 mm,C=0.8 mm.

Ideally medical devices that come in contact with a vascular wall or aredeployed endovascularly require features that ensure they do notperforate or puncture the vessel wall. Perforations can lead to hematomaand other serious adverse events. It is critical for devices to reducethe risk of internal wall damage. This also provides the clinician withconfidence to advance the device against resistance, knowing that thedevice will not induce trauma. FIGS. 101 to 104 show various bristletips to prevent vessel perforation upon or after deployment. (i) softspring 180 (FIG. 101), (ii) soft flexible tips (e.g. made from apolymer) 181 (FIG. 102), (iii) bristles at end of bristle device tied tomake an atraumatic end 182 (FIG. 103), (iv) bristles 183 naturallyprotrude from the end of the device (FIG. 104).

FIGS. 101 to 104 illustrate various embodiments of atraumatic distal andproximal ends designed to prevent vessel wall perforation

During percutaneous endovascular treatment an embolisation coil istypically delivered to a desired location in the vasculature of apatient through the use of a catheterization procedure. In thisprocedure, a catheter is inserted into the vasculature of a patient andpositioned to be proximal or distal to the targeted anatomical location.Generally, an embolisation coil is loaded into the lumen of the catheterand advanced through the catheter using a pusher rod until it reachesand exits through the distal end of the catheter.

Unless “detachable” coils are used this device cannot be repositioned orretrieved once deployed. This technique suffers from difficultyassociated with the precise and controlled placement of the embolisationcoil. Accordingly, there exists a need to develop and provide a systemor mechanism for the placement of an embolisation coil into thevasculature of a patient that can be done in a precise and controlledmanner, while maintaining cost effectiveness, simplicity, reliability,and manufacturability.

FIG. 105 (a) shows an assembly wherein the bristle device 200 isattached to a delivery wire 201 via a screw mechanism 202. In thisassembly detachment is accomplished by unscrewing the delivery wire fromthe bristle device as shown in FIG. 105 (b).

The interaction of the device, which is constrained radially at least tosome extent within the lumen, causes an interference fit. Thisinterference fit occurs due to the propensity of the lumen to try alter(reduce) the diameter of the bristle device, and the propensity of thebristle device to try to alter (increase) the lumen diameter.

The classic relation describing the holding torque of an interferencefit assembly using that the assumption that the surfaces have noirregularities and that the contact pressure at the interface isuniformly is distributed, is as follows (Mascle et al., 2011):

T_(holding)αμ_(s)d_(sh)pA

This implies that the holding torque, T_(holding), or torque required tocause a rotation of the bristle device within the lumen is proportionalto the coefficient of static friction between the bristle device and thelumen wall, μ_(s), the diameter of the lumen, the interference pressure,p, and the area of contact, A.

This implies that interference pressure is a function of the outwardradial force of the device against the pressure. The coefficient ofstatic friction between the bristle device and the lumen wall is afunction of the lumen and bristle device materials, their roughness andthe topography of the geometry which results when the bristle device isdeployed within the lumen.

In order to allow detachment of the bristle device from the deliverywire once it has been deployed in the lumen, the torque to unscrew thedelivery wire from the bristle device must not exceed the holding torqueof the bristle device in the lumen, i.e. T_(holding)>T_(unscrew). If theholding torque does not exceed the torque required to unscrew thedelivery wire from the bristle device, the bristle device will simplyrotate within the lumen and detachment may not occur.

FIG. 106 shows a bristle device 210 deployed in a lumen. Section Arepresents a cross section within the bristle device. Section Brepresents a cross section at the level of the delivery wire proximal tothe detachment mechanisms.

In FIG. 106 (b), the behaviour of the bristle device 210 is shown whenno twist is applied to a delivery wire 211 (top). The middle schematicshows the behaviour when some twist is applied to the delivery wire 211causing the bristle device 210 to rotate within the lumen (undesirable).This occurs because the holding torque of the bristle device does notexceed the torque required to unscrew the bristle device from thedelivery wire. In the bottom schematic upon rotation of the deliverywire, no rotation of the device occurs since the holding torque of thebristle device exceeds the torque required.

When coils migrate to unintended locations, they are required to beremoved to prevent non-target embolisation, tissue ischemia and/orerosion. In general removal of coils is attempted via a percutaneousendovascular approach, by placing a guiding catheter close to themigrated coils and extracted by using a forceps or gooseneck snare tograsp the coil. Technically, removal of coils is very challenging andcan take dozens of attempts with various devices to remove [22].Complications of coil retrieval are significant and can involve [8]:

-   -   Disturbing the rest of the coil nest and exacerbating the        problem.    -   Damaging other vessels: dissection, occlusion, spasm, rupture of        the vessel caused by manipulation of the retrieval device.    -   Cardiac arrhythmias if the coil has migrated to the heart.    -   Embedding or further distal embolisation of the coil or device

In the invention we provide a bristle device in which the diameter(size) of the core is greater than that of the core of the bristledevice. This enables the bristle device to be retrieved easily using agooseneck or snare type device.

FIG. 107 shows how a retrieval device 220 can easily grasp a bristledevice 221 at the screw detachment mechanism. In the top schematic theretrieval device has been deployed from its delivery catheter. In themiddle schematic the bristle device detachment mechanism has beengrasped in the wire “snare” of the retrieval device and is beingretracted into the catheter. The bottom schematic shows the finalretraction of the bristle device, now almost entirely in a collapsedcondition, into the catheter.

FIG. 108 shows a bristle device 230 with a screw detachment mechanism231 at both ends. This can be retrieved from a distal or proximalapproach.

Migrated coils are generally retrieved using a forceps or a goosenecksnares. These are expensive devices and can significantly add to theprocedural cost. Ii would be advantageous if a coil could be grasped andremoved without the necessity to use additional retrieval devices. Inthe embodiment shown in FIG. 109, the screw detachment mechanism isshaped to guide the delivery wire into the thread to be screwed to thewire and retrieved.

In some cases, it is unnecessary or undesirable to permanently occlude ablood vessel. In these circumstances, using an agent which causestemporary vascular occlusion may be preferable.

Circumstances in which temporary agents may be indicated [8]:

-   -   Pre-operative embolisation: e.g., embolisation of a renal tumor        immediately before resection. In these circumstances, there is        no advantage in permanent obliteration of the tumor circulation        and any non-target embolisation is less likely to be harmful.    -   Trauma: it is usually only necessary to arrest bleeding until a        stable clot forms and the vessel can heal.    -   Upper gastrointestinal tract hemorrhage.

Temporary embolisation agents are most beneficial when a vessel cansafely be sacrificed but permanent occlusion is not necessary (e.g.,internal bleeding associated with trauma). Having a biodegradableembolisation device that provide temporary embolisation, relieves theclinical issue, and then safely degrades over a specific time periodproviding the opportunity for systemic blood flow to be restored wouldbe a significant clinical advancement.

In other circumstances, it may be preferable that once embolisation hasoccurred, that the device, or a portion of the device, biodegradesmeaning that the implant:

1. Has no structural role integrity, and therefore does not interferewith surrounding tissues

2. Is no longer present in the body

In the invention, either the core, or the bristles, or both the bristlesand the core could be biodegradable or absorbable.

The biodegradable/absorbable elements of the device may be composed ofsynthetic polymers (Poly-lactic acid (PLA) and its isomers andcopolymers, Poly-glycolic acid [PGA], Poly-caprolactone [PCL], Polydioxanone, Poly-lactide-co-glycolide) or Magnesium alloys. This is shownin FIGS. 110 to 112.

FIG. 110 (i) a bristle device 250 on implantation, (ii) thrombus formedin the bristle device, (iii) core begins to degrade, (iv) core fullydegraded leaving only thrombus interspersed with bristles supporting thethrombus

FIG. 111 (i) a bristle device 260 on implantation, (ii) thrombus formedin the bristle device, (ii bristles begins to degrade, (iv) bristlesfully degraded leaving only thrombus a supporting core

FIG. 112 (i) a bristle device 270 on implantation, (ii) thrombus formedin the bristle device, (iii) core and bristles begin to degrade, (iv)bristle device fully degraded leaving only thrombus within the vessel

A number of methods of manufacture may be used to make the prosthesis.FIG. 113 shows a twisted wire device 280 manufactured using a twistedwire method. The fibres are placed between two parallel wires. Thesewires are fixed at one end and twisted at the other. Upon twisting thewires are formed into a helix causing the bristles to translate frombeing parallel to being rotationally offset from one another forming adevice like construct.

In another embodiment variations in the bristle density can be achievedby varying the pitch of the twisted wire which the holds the bristles inplace. This is shown schematically in FIG. 114. FIG. 114 illustrates atwisted wire device with varying core wire pitch in order to vary thedensity of the bristles.

FIG. 115 shows a series of individual segments which in this case areextrusions 290, each of which has an array of long elements projectingfrom the centre. Upon connection of these constructs, a prosthesis 295suitable for lumen occlusion can be constructed. FIG. 115 illustratesmanufacture from a series of device segments, or extrusions.

FIGS. 116 and 117 illustrates a method of manufacture in which theentire device is one piece is by cutting the fibres from a core 300.This could also be constructed by laser cutting the tube and passing andexpanding element through the lumen to splay out the fibres.

A bristle device may also be used as a platform for therapeuticdelivery. This could be an agent to augment thrombogenicity (sclerosant,fibrin, thrombin, glue, alcohol), or to delivery an oncologic drug totreat a tumour, or a device to aid in radiofrequency ablation. This isshown schematically in FIG. 118. The elution time of such an agent couldbe seconds, hours, days, or years. The coating could be fluid or solid.

FIGS. 118-119 illustrate delivery of the drug to the vessel wall once abristle device 320 is in place.

In one embodiment, the device is coated with a drug, or sclerosant, justbefore being pushed into the catheter (FIG. 120). This drug orsclerosant is then delivered to the vessel wall once it is deployed atthe target site. This is shown schematically in FIG. 120. FIG. 120illustrates flushing of bristle device with a therapeutic prior to beingpushed to target vessel. The detailed view shows a coating of the drugon the device fibres following flushing.

The bristles of the bristle device could be further enhanced usingstriations or holes which can contain a therapeutic. This could increasethe volume of therapeutic on the bristle, and to further control itselution over time by restricting the area from which the therapeutic candissolve, elute.

FIGS. 121 to 123 illustrate bristles that are enhanced using pores,striations or holes to hold drug for elution over time.

The invention also provides a “perfusion bristle device”. This bristledevice 350 contains a channel 351 through the centre for flow. As theflow passes the bristles the therapeutic is transferred to the flow,allowing a distal therapy to be delivered. FIG. 124 illustrates the useof a perfusion bristle device for delivery of a drug.

To enable the physician to deliver the bristle device through tortuousanatomy it must be flexible. This also enables the bristle device toconform to tortuous anatomy once implanted. The flexibility of theprosthesis is defined, primarily, by properties of the core to which thebristles are attached. The flexibility of the core is a function notonly of the amount of material in the core, but also its distribution,and material (lower modulus means greater flexibility).

There are certain clinical indications where the optimal clinicaloutcome would be to simultaneously embolise a vessel and an adjoining,diverging division.

Such a clinical situation is the prophylactic embolisation to preventtype II endoleak pre-endovascular aneurysm repair (EVAR). Type IIendoleaks can be identified during angiography by the presence ofcontrast travelling from a peripherally catheterized vessel into theexcluded aneurysm sac. The objective when embolising pre-EVAR ispermanent occlusion of the internal iliac artery proximal to itsbifurcation to ensure that there is complete occlusion before proceedingto EVAR, as any leak will cause reoccurrence of the issue. Using anangled, adjacent vessel to anchor a portion of the device whiledeploying the majority of the same device in the larger vessel wouldprovide an anchor for the device, preventing future migration.

Additionally, the internal iliac vein bifurcates into anterior andposterior divisions, which supply pelvic organs as well as the glutealmuscles. It is frequently necessary to embolise one of the anterior orposterior divisions as well as the internal iliac vein. The sameapproach as described previously would be advantageous; embolising theadjacent tributary while retracting the remainder of the device toocclude the higher order vessel.

A bristle device, which has the flexibility to be deployed acrossbifurcating vessels, may be preferable in these instances.

FIG. 67 illustrates two device prostheses of the same length withdifferent core wire diameters, ø₁ and ø₂, where ø1>ø₂. Note: it isassumed that the core is approximately of circular cross section. Oneend of the prostheses is fixed and a load, P, is applied to the oppositeend causing deflection of the prosthesis. The deflection of the largerdiameter device, U1, is much smaller than that of the lower diameterdevice (U2).

Considering a bristle device with a stainless steel core constructedfrom twisted wire, its diameter should preferably be constructed fromtwisted wires of diameter 0.02 inches or less. Otherwise it may not bepossible to track the device to the target vessel for deployment.

In other embodiments, the flexibility of the device could be improved byhaving flexible sections 95 between device sections 96 as shown in FIG.68. Bending within the device is taken up, primarily, by the flexiblesections, which can articulate to enable it to pass through a catheterplaced in tortuous anatomy, or to be deployed in a curved vessel, oracross a bifurcation. In this case the bristle device has flexiblesections for articulation.

Because the device is flexible it will not perforate a vessel or causeinjury to the patient. A device which is not flexible may cause injuryduring deployment.

Furthermore, physicians may wish to place a portion of the device in amain vessel, and another portion of the device in a branch asillustrated in FIG. 68. Depending on the angle between the main vesseland the branch of the vessel, the implant is sufficiently flexible toaccommodate the anatomy at the location in which it is deployed.

Many vessels in the body undergo significant deflections during normalmovement such as when walking or sitting. The embolisation device of theinvention has sufficient flexibility and durability such that it willnot fracture, or perforate the vessel or neighbouring anatomy duringsuch movements.

The embolisation device may be constructed such that it is extremelyflexible. One way to achieve this is by connecting segments of brushesto one another via more flexible sections such as illustrated in FIG.68. The flexible sections may be introduced as unique parts, or byconnecting the segments with connections that provide articulationand/or regions to accommodate bending.

For example, as illustrated in FIGS. 127 to 129, an embolisation device500 is shown which has loops 501, 502 on adjacent stem segments. Theloops 501, 502 are interconnected, such that the device can flex atthese connections easily. These connections act as articulating points,at which one bristle segment is hinged to the next. This ensures thatbending during movement is easily accommodated without potential fordevice fracture. In addition such connections ensure that the devicecannot substantially elongate or compress during delivery. Referring toFIG. 130, in this case there are flexible connections between shorterstem segments for enhanced bending movement.

FIGS. 127 to 130 illustrate bristle devices for delivery into a bodylumen comprising a stem and a plurality of flexible bristles extendinggenerally radially outwardly from the stem. The device comprises aplurality of segments, each of which comprises a plurality of bristlesextending generally radially outwardly from the stem. At least some ofthe segments are spaced apart to define spaces therebetween toaccommodate bending of the bristles. This bending of the bristlesenables the device to be deformed into a collapsed condition, so thatthe diameter in the collapsed condition is smaller than would be thecase if such spaces were not present between the segments.

Use of Single Wire of the Stem FIG. 131.

Often a bristle brush stem is constructed from two wires twistedtogether. A region of increased flexibility can be constructed bydiscontinuing one of the wires while continuing the other, thusdecreasing the stiffness between adjacent brush sections.

Use of Single Wire of the Stem FIG. 132,

In another embodiment, a suture or monofilament material much less stiffthan the bristle brush stem may be used to connect brush segments,providing improving flexibility and articulation points. This suture maybe connected to the brush segments using a hypotube. This hypo tube maybe attached to the bristle brush stem and suture by crimping.

Spring Connection—FIG. 133.

In another embodiment, a spring connection between individual brushsegments may be used to improve the flexibility in the device. Thisspring may be configured such that in the unloaded configuration itcannot compress. This means that the device cannot substantiallydecrease while being pushed through the catheter.

Alternatively, the spring may be configured such that the spring cancompress or elongate, enabling the physician to adjust the total devicelength as he deploys the device.

Spring with Tension Wire—FIG. 134.

In some instances, it may be desirable to limit the maximum length ofthe device. The maximum extension of the spring-like connection abovecould be limited by the inclusion of a tension wire, which is connectedto each segment of the bristle brush. The spring enables bending of theflexible connection, while the tension wire prevents elongation of thedevice when under tensile loading.

In another instance the device the spring may be configured such thatthe spring can, enabling the physician to reduce, but not increase thetotal device length.

O-Ring—FIG. 135.

In another configuration a ring may be used to connect bristle brusheswith looped ends. This ring may be constructed from a stiff material,enabling a hinge type joint, or a flexible material in which the ringalso flexes during bending of the device.

Simple Wire—FIG. 136.

In another configuration, a wire or string connection, of a much lowerstiffness than the bristle brush stem may be used. This wire, because ofits lower material stiffness, and/or lower diameter will accommodatebending of the device. The wire or string may be connected to the endsof the bristle brush by an adhesive or weld or solder, or it may becrimped in place by the adjacent wires of the stem of the bristle brushsegment.

Connector Element Between Loops FIG. 137.

In another embodiment, looped ends of the bristle brush stem may beconnected via a connector element. This element is configured such thatits arm or arms on one end, can be bent to a configuration enabling themto pass through the loop. These loops return to the unloadedconfiguration, meaning they cannot pass back through the loop. A similarconfiguration exists on the other end of the connector, connecting it tothe adjacent bristle brush segment with a looped end.

Connector Element Between Loops—FIG. 138.

Another configuration utilises a wire/string element, woven between thetwisted wire stem of the bristle brush segment. This wire/stringelement, which is more flexible than the stem, emerges from the end ofthe bristle brush segment, and connects to the next bristle brushsegment. A gap between the two bristle brush segments enables thewire/string element to accommodate deformations easily.

Suture/Mono-Filament Connection Between Loops—FIG. 139.

A thread type connection may also be made between adjacent loops ofbristle brush segments. This thread may be made from a wire, a polymermono-filament or suture.

Elastomer/Polymer Tube Connections—FIG. 140.

An elastic tube, wherein the inner diameter of the tube is smaller thanthe outer diameter of the bristle brush stem. When the elastic tube ispushed onto the end of the bristle brush stem, an interference fitoccurs, anchoring the elastic tube to the stem. This elastic tube isanchored to two adjacent bristle brush segments, enable articulationbetween them.

Alternatively, the elastic tube may be a heat shrinkable material, whichwhen subject to heat reduces its diameter to adhere to the stem of theadjacent brush segments.

Braid Connection—FIG. 141.

In another embodiment, a braid may be used to connect the bristle brushsegments.

Elastomer/Polymer Tube Connections—FIG. 142.

A slotted tube may also be used to connect the segments. When under abending load, the slots can open to accommodate the articulation. Theslotted tube may be connected to the stem by crimping or welding orsoldering.

Migration may be defined as the movement of an implant from its targetvessel location to another location in the vasculature. It is a knowncomplication of embolisation procedures. Since the direction load on anydevice placed in the vasculature is dependent, at least in part, on thedirection of blood flow, it is intuitive that a device may be optimisedto prevent migration depending on flow direction.

Veins return the blood flow towards the heart, while arteries carryblood away from the heart. This means that a device implanted in a veinis most likely to migrate towards the heart, while a device implanted inan artery is most likely to migrate away from the heart to a more distalvessel.

A bristle brush embolisation device may be deployed such that itsbristles are oriented to prevent, in so far as possible, migration in agiven direction. For example the optimal bristle direction for a devicedeployed in a vein, to prevent migration, is such that the ends of thebristles are pointing towards the heart (FIG. 143). This is because eachindividual bristle ends will interact with the vessel wall, increasingfriction, and preventing migration in that direction. The opposite istrue for a bristle brush deployed in an artery. In that case, thebristles should point away from the heart (FIG. 144).

In another configuration, some, or a portion of the bristles may pointin both directions such that the device is adapted for use in either avein or artery.

To ensure that the bristles are pointing towards the heart for venousindications, the device can be pushed into a delivery catheter. As thebristle brush is pushed into the catheter, reducing its diameter to acollapsed configuration, the bristles will point proximally. However,manipulation of the device while pushing into a catheter, may causedamage to the device.

To enable the physician to orient the bristles to point towards or awayfrom the heart, the following loading and delivery system may beprovided.

The loading system comprises a loading tube 600 having a distal endwhich can be connected to a guide catheter 601. The loading tube 600 maybe adapted to enable flushing of the device.

The loading system may also comprise a loading wire 602, which can beattached to a distal end 615 of the implant, in this case anembolisation device 500. The loading wire 602 has an end with anengagement 620 feature to engage the distal end 615 of the implant usingany suitable mechanism such as via a threaded connection 605 or ahook/loop mechanism 610.

A delivery wire 603 having a distal end 60 which can attach to theproximal end 616 of an implant may be used to push the implant throughthe loading tube 600 into a guide catheter 601 and on to the targetvessel site.

The bristle brush embolisation implant 500 may have a distal end 615which can be connected to the loading wire 602 (for use in venousvessels) and a proximal end 616 which can be connected to a distal end625 of the delivery wire 603.

Use in Arterial Vessels (FIGS. 149 to 153)

The device 500 may be used in an artery as follows:

The distal end 625 of the delivery wire 603 is attached to the proximalend 616 of the implant 500.

The proximal end of the delivery wire 603 is inserted through the distalend of the loading tube 600 (FIG. 149) and threaded through to the otherend of the loading tube 600. The delivery wire 603 is further pulleduntil the implant 500 is completely within the loading tube 600 (FIG.150).

The loading tube 600 is connected to the guide catheter 601.

The bristle brush implant 500 is pushed, using the delivery wire 603,into the guide catheter 601 and on to the target vessel 611 (FIG. 151).The implant 500 is deployed by continuing to push on the delivery wire603 and/or drawing back the catheter 601 as illustrated in FIGS. 152 and153.

Use in Venous Vessels (FIGS. 154 to 160)

The end 620 of the loading wire 602 is connected to the distal end 615of bristle brush implant (with a hook on the end 620 of the loadingwire, and a loop 615 on the distal end of the implant 500). The distalend 625 of the delivery wire 603 is connected to the proximal end 616 ofthe bristle brush implant 500.

The end of the loading wire 602 not connected to the bristle brush 500is inserted through the proximal end of the loading tube 600 andthreaded through to the other end of the loading tube 600.

The loading wire 602 is further pulled until the distal tip of thebristle brush implant 500 is just visible outside the distal end of theloading tube 600.

The loading wire 602 is detached from the implant 500 (FIG. 156).

The distal end of the loading tube 600 is connected to the proximal endof the guide catheter 601.

The implant 500 is pushed into guide catheter 601 and on to a targetvessel 611 using the delivery wire 603. The implant 500 is deployed bycontinuing to push on the delivery wire 603 and/or draining back thecatheter 601 as illustrated in FIGS. 157 and 158. After deployment thedelivery wire 603 is disconnected from the implant 500.

In one embodiment, the distal end 615 of the implant has a loopconfiguration for connection to a hook on the end 620 of the loadingwire 602, while the proximal end 616 has a threaded end. In anotherembodiment, both ends are threaded.

The loading wire 602 may be used to ensure that only some of thebristles point in one direction, while the others point in the opposingdirection. This is achieved by pulling the bristle brush implant, usingthe loading wire 602, beyond the point wherein only the distal tip ofthe implant protrudes out of the distal tip of the loading tube 600.This allows a portion of the bristles to emerge from the loading tube600. The delivery wire 603 is then used to pull the implant back intothe loading tube 600, reversing the direction of this portion of thebristles.

For embolisation it is preferable that the device be oversized to ensureit is anchored safety in the vessel, preventing migration. For thisreason all segments of the device should be of a greater diameter thanthe target vessel. This ensures that the entire vessel lumen is treatedand forms a clot, and also that the device cannot migrate.

In order to further prevent migration of the device one or more fibresegments may be added to the device which have enhanced resistance tomigration. In such a configuration, an individual segment, or segmentsmay have different mechanical properties to other segments on thedevice. Preferably this segment, which will be referred to as an anchorsegment, is configured so as to also occlude, although perhaps not asrapidly or efficiently as adjacent segments.

This anchor segment may be achieved via increased fibre diameter toincrease stiffness, or by use of a stiffer material. Preferably asuper-elastic material such as Nitinol is used due to its ability toaccommodate large changes in vessel diameter post-implantation. Anotheradvantage of a super-elastic material is that it will not becomeshape-set if left too long in the catheter, which can occur for manypolymers. Furthermore although the anchor segments may utilise ametallic material the other segments may be constructed from a polymermaterial; thus reducing artefact under imaging such as MRI or CT.

In one configuration a segment 700 to help anchor the device withincreased fibre diameter or material stiffness may be at the proximalend of the device (FIG. 159). In another configuration, the anchorsegment 700 may be at the distal end of the device (FIG. 160).Alternatively the anchor segment 700 may be placed at both the distaland proximal end of the device (FIG. 161).

In yet another configuration the anchor may be configured such that thefibres in the anchor segment 700 are longer than other segments 701.These fibres may or may not have the same stiffness or diameter ofadjacent segments. This is advantages particularly in veins which can besubject to large, temporary vessel distension (e.g. during Valsalva).The other segments 701, with a lower diameter, intended for occlusionare sized according to a lower diameter related to the more permanentvessel state (not distended due to Valsalva). This enables a more densenumber of fibres to be delivered through the catheter in segments 701with a lower diameter enhancing vessel embolisation. The anchor segments700 will also induce clot formation, albeit potentially at slower rate.Such an anchor segment 700 could be placed at the proximal end of adevice (FIG. 162), distal end (FIG. 163) or both proximal end of thedevice (FIG. 164).

An anchor segment 700 could also be placed within the devicemid-section, that is, neither the most proximal nor distal segment. FIG.165 shows such a configuration with long fibres.

Individual segments with differing groups of bristles within the segmentmay also be utilised. Such segments will have fibres optimal for bothanchoring and promotion of clot. These longer fibres could be configuredsuch that they forma diamond or stepped geometry. In one configuration aseries of segments are shown which have longer fibres 700 in themid-section of the segment, and shorter fibres at the proximal anddistal ends of the segment (FIG. 166). These longer anchoring fibres 700may or may not be of the same stiffness or material as the adjacentfibres in the segment.

The fibre length in segments 705 may taper from the proximal to thedistal end of individual segments, or from the distal to the proximalend (FIGS. 167 and 168).

In cases where the fibres in a segment are of Nitinol, the fibres may beshape-set (via a heating and annealing process) to achieve preferablegeometries. In one embodiment, the fibres are shape-set such that theydo not project at approximately 90° from the core of the device 710. Inone embodiment the fibres are shape set that the ends of the fibrespoint distally, i.e. from the catheter tip (shown in FIG. 169). Thisenables easier loading of the device 710 into a loading tube or acatheter for delivery as the fibres are preferably oriented for entryinto tubular component. In another embodiment the fibres are shape-setsuch that some fibres point proximally, while other fibres pointdistally. In another embodiment, the fibres are shape set such that akriss-crossing pattern is achieved reducing the aperture betweenadjacent fibres tangentially and thus improving thrombogencity.

The invention may also be used for the treatment of aneurysms (neuro orperipheral). In one configuration, a single segment 715 may be deployeddirectly into the aneurysm sac (FIG. 170). In another two segmentsseparated by a flexible, spring, or elastic element. In this case whendeployed the elastic member will ensure interaction of the fibres withthe vessel wall such as to help anchor the device in the aneurysm. Thisis shown in FIG. 171. This may be particularly advantageous in the caseof wide-necked aneurysms.

In another approach a number of segments 715 could be delivered into theaneurysm sac such that they fill the entire space efficiently. In thistype of scenario the individual fibres will interact with one anothercausing a dense scaffold which cannot straighten out or fall back intothe parent vessel (FIG. 172).

The invention may further be used for the treatment of aneurysms via theparent vessel. In this situation the objective may be to occlude theentire parent vessel (FIG. 173). Once a clot has formed in the device720 supply to the aneurysm sac is cut off, preventing a rupture andcausing clot formation within the aneurysm sac. In another approach theentire parent vessel may be treated with a number of segments 725, 726which are not connected and placed in the parent vessel distal andproximal to the aneurysm (FIG. 174). In one embodiment the two segments725, 726 could be connected by an element 727, enabling the physiciandeploy a single device which results in segments distal and proximal tothe aneurysm. In one embodiment this connecting element may beadjustable in length allowing the physician to accommodate a range ofdistances between proximal and distal ends of the device (FIG. 175).

In one method a sclerosant, glue or other embolic 730 may be injectedvia a catheter 731 between the segments 725, 726 promoting rapidembolisation of the aneurysm (FIG. 176).

In another embodiment, the device may be used to treat an endoleak. Anendoleak is a leak into an aneurysm which has been treated with avascular graft. Type II endoleaks are of then of a form where there is avessel flowing into and out of the aneurysm. In this case the physicianmay treat the aneurysm sac using many coils and the in-flow/outflowvessels. A device such as that shown schematically in FIG. 172 may beused to treat the aneurysm sac. Since the sac is typically large, thesegments 740 to be placed within the sac will preferably incorporatemuch longer and softer fibres than would normally be used in adjacentvessels. Additional devices 741 may be placed in the inflow and outflowvessels. Alternatively a configuration in which the devices comprisessegments specifically to fill and cause occlusion on the aneurysm sacmay be used, and segments which anchor the device in the in-flow outflowvessels. This is shown schematically in FIG. 177.

In some cases the physician may wish to choose the number of segmentswhich are implanted as the procedure progresses. In this case it may beadvantageous to have a number of segments 750 available in the catheter751 which can be delivered at will. This is shown schematically in (FIG.178). In this figure all segments 750 are not connected, nor is adelivery wire attached. Instead a push-wire 752 is used to push thesegments 750 through the catheter 752. This allows one-by-one deploymentof the segments 750.

In one embodiment, there is a temporary interlocking connection betweenadjacent segments. The most proximal segment is connected the deliverywire by an interlocking connection. This enables the physician to pushand pull the segments while they are still within the catheter. Once asegment is pushed out of the catheter its temporary interlockingconnection is undone, enabling it to detach from the adjacent proximalsegments. At any stage prior to the proximal interlocking portion of asegment exiting the catheter tip, it can be retracted by retracting thedelivery wire.

It may be preferable to enhance the thrombogencity of the device bymodifying the Nylon fibres by etching. This increases surface roughnessincreasing surface area and propensity for platelet adhesion. Nylonfibres are etched to increase the surface roughness thus increasingthrombogencity. This etching may be achieved using by immersing thefibres in a solution of 75 parts potassium dichromate, 1250 partssulphuric acid and 120 parts water.

In some cases it may be preferable for the physician to be able to passa catheter 760 through a device 761 once delivered. The ease of passinga catheter 760 through the device may be improved by offsetting the stemcore 762 of the device towards the outer diameter of the device, suchthat the fibre length varies about the stem circumference as shown inFIG. 179. This is shown in cross section in FIG. 180. In one embodimentin some regions about the circumference there are no fibres present, orthe fibres are trimmed to a length close to zero. In anotherconfiguration two parallel segments or devices of this type could beconnected for enhanced occlusion (shown in cross section in FIG. 181).

A method may be used wherein a device is used to prevent backflow, knownas reflux, of particles delivered during particle embolisation. Theseparticles may be used to cause end-organ tissue neucrosis or for thedelivery of radio-embolisation or chemo-embolisation. One example is thetreatment of uterine fibroids using particles, in which the objective isto send as distally as possible until they become trapped in themicrovasculature (see FIG. 182). These particles can damage other areasof the body if allowed to leave the target vessel or end organ. Whenused, the intent is to deliver the particles until stasis is achieved.Once this occurs it is a problem that particles can flow backwards andtravel to non-target locations.

Placement of a bristle brush device will prevent these particles fromtravelling proximally once stasis occurs as the particles will becometrapped in the fibres. To deliver the particles a catheter 760 is passedthrough the bristle brush 761, and particles then injected through thecatheter 760 (FIG. 183).

Preferably this type of device 761 will be constructed so as to allowblood flow for a period of time (enabling the particles to traveldistally to the target location), and eventually occlude once theparticle delivery is complete. In one approach the bristle brush may beremoved once the particle embolisation is complete.

The device disclosed may also be used for the treatment of saphenousveins for the treatment of lower limb varicose veins. It is welldescribed that failure at the sapneous vein junction is important andthat an implant or permanent ligation at this location would preventrecurrence. A permanent or biodegradable fibre device may beparticularly advantageous for prevention of these failures.

A method may be used in which an embolisation device 775 is firstdeployed into a saphenous vein 770 under ultrasound. The device maytreat the entire length, or a significant portion of the length, of thesaphenous vein. A sclerosant agent or other embolic or glue may then beinjected by the physician along the length of the device, treatingperforators and collaterals. This is shown schematically in FIG. 184,185.

In another method (FIG. 186) a short device 780 may also be placed atthe cranial end of the saphenous vein. A scloerosing agent may beinjected in the caudal portion with the device preventing cranialmigration of the embolic into non target vessels.

The device may be left permanently in the saphenous vein or retrievedinto the catheter for removal once the procedure is complete.

Generally this is a procedure will be performed under ultrasoundimaging. It is therefore preferable that the device be comprised ofechogenic materials, or have an echogenic coating, to enable thephysician the device during placement. In particularly the stem may becomprised of an echo-genic material. More preferably echogenic markersmay be placed at the proximal and distal ends of the device.

In one embodiment the device is configured so as to control the embolicto remain between the device ends. In another embodiment the device isconfigured so as to allow caudal flow the sclerosant but not cranialflow.

To enable efficiency in manufacture, the looped end of a segment may beconnected to an adjacent segment by means of modular unit 790 as shownin FIG. 187. This modular unit 790 is configured so as to have an openconfiguration to enable it to be connected through the loop 791 of theadjacent segment. This is then closed by mean of a crimp or weld makinga permanent flexible connection between adjacent segments 792 as shownin FIG. 188.

In another embodiment the segments 792 may be manufactured so as to nothave loops at either end. A modular unit 795 of two interconnected loopsmay be used to connect the segments by means of crimping or welding orother (FIG. 189, 190).

In one embodiment the modular unit may be constructed from a wire andhypotube. In another embodiment the modular unit may be constructed froma single cut hypotube cut and formed into a suitable shape.

Although the bristle brush segments can embolise a vessel, a clot mustbuild within the scaffold which takes time to occur. In one embodiment aflow restrictor such as a membrane 800 may be included on the proximalend of the device restricting blood flow into the device and causingstasis. The more distal fibre segments further promote embolisation, andanchor the device in the vessel along the target vessel. Although afocal occlusion may be sufficient at the proximal end due to the effectof the membrane 800, it is frequently the case that a physician wishesto embolise a vessel length due to the presence of collaterals oraneurysm.

The membrane 800 may be impermeable in order to constitute a completeflow blocker. This ensures rapid cessation of the in-flow causing stasisalong the vessel length. This encourages more rapid generation of clotwithin the fibre scaffold along the target vessel length.

The membrane 800 may be comprised of self-expanding material to ensurethat it expands to fill the vessel lumen upon deployment. In anotherembodiment the adjacent fibres of the most proximal fibre segment movethe membrane form the collapsed to the expanded state upon deployment.The membrane may be of a disc shape and placed at the proximal end ofthe device (as shown in FIGS. 191 to 193), or at the distal end of adevice, or at both ends of the device.

In some cases a membrane 805 may have a number of slots 806 tofacilitate folding of the device for when collapsed in a deliverycatheter, and to ensure a more uniform expansion (FIG. 194). In anothercase a membrane 809 may comprise a number of layers, with (FIG. 197) orwithout slots. The layers may have the same or different diameter. Inone embodiment the more distal layer has a lower diameter than the moreproximal layer. In another embodiment a membrane 810 may be comprised ofa number of overlapping leaflets or petals 811 (FIG. 195). Thisoverlapping construction further improves folding and prevents formationof gaps when deployed in the vessel due to non-uniform expansion of themembrane.

A membrane such as a disc may be treated so as to have predefined foldsto aid collapse for delivery, and provision of a seal against the vesselwall upon deployment.

In one embodiment, if placed at the proximal end of the device, themembrane is collapsed by the catheter or loading tube tip duringretraction into the catheter or loading tube. Upon deployment the fibresdistal the membrane expand the membrane out to meet the vessel wallrestricting flow.

In one configuration a membrane 815 may be placed within the fibresegment such that there are fibres both immediately distal and proximalto the segment (FIG. 196). These fibres serve to support the membraneduring loading and deployment ensuring that it is collapsed and expandedin a controlled way

In some cases membrane may have a diameter which is greater than or lessthan the segment diameter. FIG. 198 shows a membrane 820 with a diameterlower than the segment diameter. In this situation, the membranediameter must be at least that of the target vessel. In anotherconfiguration the membrane may be comprised of a number of layers ofdifferent diameters which may be greater than the segment diameter (FIG.197) or less than the segment diameter.

In another configuration, a membrane 825 may constitute a wind-sock typegeometry which surrounds some or all of the fibres of a segment (asshown in FIG. 199). To ensure sufficient flow restriction the wind-sockdiameter should be at least that of the target vessel. In anotherembodiment, a balloon type geometry may be incorporated. In this case afibre segment may reside within the balloon. Upon deployment from thecatheter, the expansion of the fibres from a collapsed condition causeopens the balloon up to fill the vessel lumen causing a flowrestriction.

In yet another configuration, a membrane 830 may be supported by anumber of struts 831 to control expansion and contraction duringdeployment and loading, further aiding a reliable flow restriction ofthe lumen. This is shown schematically in FIG. 200. These struts may bemade from Nitinol.

In one embodiment the edges of the membrane incorporate frayed edges tohelp ensure a seal against the vessel lumen.

The membrane may be comprised of a film, weave, braid or fabricconstruction. Suitable materials include PTFE, Nylon, PET, PEEK,Polyurethane, Polypropylene and Silicon. A fine Dacron mesh may also beused.

A membrane may be manufactured in-situ on a fibre segment by dipping ofsome or a portion of the device in silicone or another elastomer. Whencured the webbed effect and membrane will be formed between the fibres,acting as a membrane to aid flow restriction.

In one embodiment the fibres are interconnected with an array of microfibres ‘a web’. These microfibers increase the blood contact surfacearea and reduce aperture size to facilitate rapid occlusion The ‘web’may be manufactured by extruding the microfibers onto the brush, weavingthe microfibers through the brush fibres and/or using an adhesive toattach the microfibers to the brush fibres.

A process known as electrospinning may also be used to position themicrofibers on the brush.

The occlusion performance of a fibre segment 840 may be further enhancedby the addition of fibres to cross the existing fibres (FIG. 201). Inone embodiment a uniform distribution of fibres is added. In anotherembodiment the density of the added fibres increases towards the outerdiameter of the segment. This is preferable since as the distance fromthe stem increase, so too dos the distance between the fibres, reducingthe efficiency of blood clot formation. This could be achieved byelectro spinning. In one embodiment the added fibres are of a lowerdiameter than the other fibres in the segment. In another embodimentthey are of the same or a larger diameter. The fibres may only be addedto the distal and proximal ends.

As the objective of the invention to promote a blood clot, the number offibres which can be fitted into a catheter must be maximised to ensureembolisation. Depending on the fibre diameter, more fibres can be fittedinto the delivery catheter. This is shown schematically in FIGS. 202,203. More fibres mean a greater surface area for platelet and clotadhesion, and a smaller gap between adjacent fibres. A smaller gapbetween adjacent fibres means that the distance or thickness of thrombuswhich must form is lower in order for adjacent thrombus to meet.

Typically catheters have an internal diameter of 0.038, 0.056, and 0.068inches for guide catheters 4, 5, 6 French respectively. Smallermicro-catheters 0.022 to 0.028 also exist. The length of the fibresegment, gap between fibre segments and fibre density must be tuned toensure that a device can be pushed through the catheter without becomingstuck.

The stem of the device is typically constructed from a two wires (asshown in FIG. 113) or from a single continuous wire bent so as toachieve two parallel wire sections. A series of fibres is placed betweenthe wires. One end of the wire(s) is fixed while the other is twisted toachieve a cylindrical brush segment. This twisting action results in astem, the diameter of which is related to the diameter of the wire used.The stem diameter chosen must have enough strength to securely hold thefibres in place once twisted without causing a major increase in theprofile particularly when loaded in a catheter. Preferred stem wirediameters are outlined in the table below.

The table below outlines ranges of fibre density, diameter, stemdiameter, segment length and gap length according to FIG. 204 which maybe used in the invention. Devices with a lower density of fibres thanthis will not be efficient in promoting clot formation, particularly inlarger diameter vessels.

The density of the fibres is the number of fibres present per cm ofsegment length. For example in a segment of 6 mm in length, with adensity of 100, there will be 60 fibres.

Approximate Segment Gap Fibre Maximum Fibre Density Gather ID Stem WireDiameter Length Diameter Segment (number per cm of (inches) Diameter(mm) (mm) (in) Length (mm) segment length) 0.023 0.003-0.006 3-6 1-30.001-0.002 3-4 100-200 0.038 0.003-0.008 6-8 ≥2 0.002-0.003 3-7 100-3000.056 0.004-0.012  8-10 ≥2 0.002-0.003 3-7 100-800 0.056 0.004-0.01210-12 ≥2 0.002-0.003 3-7 100-800 0.056 0.004-0.012 12-16 ≥2 0.002-0.0043-6 100-800 0.068 0.004-0.012 10-18 ≥2 0.002-0.004 3-6 100-400 0.0780.004-0.012 10-24 ≥2 0.002-0.005 3-6 100-400

In some particular embodiments the following are deliverable through acatheter, but are also efficient in promoting clot formation. Deviceswith a lower density of fibres than this will not be efficient inpromoting clot formation, particularly in larger diameter vessels.Specific details are outlined in the table below.

Fibre Density Segment Segment Maximum (number Approximate Stem Diameter,Diameter, Gap Fibre Segment per cm of Cather ID Wire Occluder AnchorLength Diameter Length segment (inches) Diameter (mm) (mm) (mm) (in)(mm) length) 0.023 0.004 4-5 4-6 1-3 0.001-0.002 3-4 100-300 0.0380.006-0.008 6 8 ≥2 0.002-0.003 3-6 100-300 0.056 0.008-0.010 12 15 ≥30.002-0.003 4-5 300-800 0.068 0.008-0.012 15 17 ≥3 0.002-0.004 3-6200-800 0.078 0.008-0.012 18 22 ≥3 0.002-0.004 3-6  200-1000

Where segments are longer than 6 mm, for the densities and segmentdiameters required, it will not be possible to deliver the segmentsthrough the catheter inner diameters outlined.

The device may be comprised of one type of segment whereby each segmentis of equal efficiency in terms of both anchoring and occlusion.

In one configuration two different segments types may be used, bothintended to both anchor the device and cause occlusion, but one which ismore optimal for anchoring while the other is more optimal forocclusion.

In one configuration the device may comprise only one segment. Thesegment may be configured so as to have a variable diameter along itslength with increased fibre length at the distal or proximal end, orboth. In another embodiment a single segment has a denser fill at theproximal end and/or distal end than at the mid-section. In yet anotherembodiment more than one diameter is used for the fibres such that somefibres serve to anchor the device while other fibres better promoteocclusion.

In another embodiment, the device may be configured so the segment orsegments contain different fibre types wherein one type is more optimalfor anchoring while one type is more optimal for occlusion.

In another embodiment a membrane enhance immediate flow restriction maybe placed towards or at the proximal or distal, or both ends of thedevice.

The invention provides various embolisation devices for promoting clotformation in a lumen comprising a stem and a plurality of flexiblebristles extending outwardly from the stem, the bristles having acontracted delivery configuration and a deployed configuration in whichthe bristles extend outwardly from the stem to permanently anchor thedevice in a lumen. Referring for example to FIGS. 205 to 208 theembolisation devices 900 are first loaded into a delivery catheter whichis inserted into a target vessel 902. The device 900 is deployed. Insome cases the device 900 is mounted on a delivery wire 903 which isdetached from the device 900 after deployment. The bristles of thedevice 900 are anchored in the lumen 902 and promote clot formation(FIG. 207) until the vessel is completely occluded (FIG. 208).

Modifications and additions can be made to the embodiments of theinvention described herein without departing from the scope of theinvention. For example, while the embodiments described herein refer toparticular features, the invention includes embodiments having differentcombinations of features. The invention also includes embodiments thatdo not include all of the specific features described.

The invention is not limited to the embodiments hereinbefore described,with reference to the accompanying drawings, which may be varied inconstruction and detail.

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The invention claimed is:
 1. An embolization device loading system, theloading system comprising: (a) a bristle device, the bristle devicecomprising: (i) a stem, the stem comprising a proximal segment and adistal segment, the proximal segment comprising a first plurality ofbristles extending outwardly from the stem of the proximal segment, andthe distal segment comprising a second plurality of bristles extendingoutwardly from the stem of the distal segment, wherein the secondplurality of bristles are longitudinally spaced from the first pluralityof bristles; and (ii) a flow restrictor comprising a membrane, the flowrestrictor extending outwardly from the stem, wherein the flowrestrictor is coupled to the stem at a position located longitudinallywithin one of the first plurality of bristles and the second pluralityof bristles such that there are bristles of the one of the firstplurality of bristles and the second plurality of bristles bothimmediately distal and proximal to the flow restrictor; (b) a loadingtube; and (c) a loading wire for loading the bristle device into theloading tube.
 2. The embolization device loading system of claim 1,wherein the flow restrictor has a contracted configuration and anexpanded configuration.
 3. The embolization device loading system ofclaim 1, wherein the flow restrictor is located longitudinally withinthe first plurality of bristles of the proximal segment of the stem. 4.The embolization device loading system of claim 1, wherein the flowrestrictor is located longitudinally within the second plurality ofbristles of the distal segment of the stem.
 5. The embolization deviceloading system of claim 1, wherein the flow restrictor membranecomprises a flexible material.
 6. The embolization device loading systemof claim 1, wherein the flow restrictor membrane comprises a polymericmaterial.
 7. The embolization device loading system of claim 6, whereinthe flow restrictor membrane comprises an elastomeric material.
 8. Theembolization device loading system of claim 1, wherein the flowrestrictor membrane comprises a film.
 9. The embolization device loadingsystem of claim 1, wherein the flow restrictor membrane is impermeable.10. The embolization device loading system of claim 1, wherein the flowrestrictor membrane has a disk shape.
 11. The embolization deviceloading system of claim 1, wherein the flow restrictor membrane has aconical shape in the expanded configuration.
 12. The embolization deviceloading system of claim 1, wherein the first plurality of bristlesextend circumferentially from the proximal segment of the stem and thesecond plurality of bristles extend circumferentially from the distalsegment of the stem.
 13. The embolization device loading system of claim1, wherein the first plurality of bristles have a collapsedconfiguration in which each of the bristles of the first plurality ofbristles point proximally, and the second plurality of bristles have acollapsed configuration in which each of the bristles of the secondplurality of bristles point distally.
 14. The embolization deviceloading system of claim 1, wherein the first plurality of bristles havean expanded configuration in which the bristles extend generallyradially outwardly from the proximal segment of the stem, and the secondplurality of bristles have an expanded configuration in which thebristles extend generally radially outwardly from the distal segment ofthe stem.
 15. The embolization device loading system of claim 1, whereinthe first plurality of bristles have an expanded configuration whereinthe bristles extend partially in a first longitudinal direction and thesecond plurality of bristles have an expanded configuration wherein thebristles extend partially in a second longitudinal direction which isopposite to the first longitudinal direction.
 16. The embolizationdevice loading system of claim 1, wherein the first and second pluralityof bristles comprise flexible bristles.
 17. The embolization deviceloading system of claim 1, wherein the stem further comprises aconnector coupling the proximal segment of the stem to the distalsegment of the stem.
 18. The embolization device loading system of claim17, wherein the connector is flexible.
 19. The embolization deviceloading system of claim 17 wherein the connector is a tube coupled to adistal end of the proximal segment such that the distal end of theproximal segment is positioned within the tube and a proximal end of thedistal segment such that the proximal end of the distal segment ispositioned within the tube.
 20. The embolization device loading systemof claim 17, wherein the connector is extendable.
 21. The embolizationdevice loading system of claim 1, wherein a spacing between the firstplurality of bristles and the second plurality of bristles defines a gapdistance and wherein a spacing between each of the longitudinallyadjacent bristles within the first and second plurality of bristles isless than the gap distance.
 22. The embolisation device loading systemof claim 1, wherein the bristle device is configured to cause denudationto an endothelium of a lumen wall.
 23. The embolisation device loadingsystem of claim 1, wherein the membrane comprises an expanded diameter,which is smaller than an expanded diameter of the one or more the firstplurality of bristles and the second plurality of bristles.